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Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Patients With Advanced Cancer

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ClinicalTrials.gov Identifier: NCT01347866
Recruitment Status : Terminated (Refer to Detailed Description for documentaion of Termination Statement.)
First Posted : May 4, 2011
Results First Posted : October 29, 2018
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Advanced Cancer
Interventions Drug: PF-05212384
Drug: PD-0325901
Drug: irinotecan
Enrollment 105
Recruitment Details  
Pre-assignment Details In Arms A and B, 7 and 14 participants were screed and received study treatment, respectively. In Arm C, 45 participants were screened and 44 received study treatment. In Arm D, 39 participants were screened and 37 received study treatment. There was no Stage 2 for Arm D, the study was terminated before enrolling patients to Stage 2 for Arm D.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+ PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Period Title: Overall Study
Started 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Reason Not Completed
Death             0             0             0             1             2             2             1             0             4             1             3             1             2             0             0             1             0
Lost to Follow-up             0             0             0             0             0             0             0             1             1             0             0             0             0             0             0             0             0
Other             3             1             1             4             5             0             5             3             22             5             0             3             4             4             2             3             0
Subject refused further follow-up             2             0             0             2             0             1             0             0             4             1             0             0             1             3             1             0             2
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+ PD-0325901: Arm D1B (Stage 1)) PF-05212384+ PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1) Total
Hide Arm/Group Description Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Total of all reporting groups
Overall Number of Baseline Participants 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2 102
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 1 participants 1 participants 7 participants 7 participants 3 participants 6 participants 4 participants 31 participants 7 participants 3 participants 4 participants 7 participants 7 participants 3 participants 4 participants 2 participants 102 participants
58.8  (8.7) 54.0  (0.0) 49.0  (0.0) 53.6  (14.1) 59.1  (12.9) 67.0  (3.6) 60.8  (7.2) 63.3  (14.5) 56.7  (12.4) 63.3  (5.9) 43.3  (9.1) 64.0  (8.9) 55.7  (10.0) 57.9  (12.9) 61.3  (14.2) 60.0  (11.8) 54.5  (9.2) 58.5  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 1 participants 1 participants 7 participants 7 participants 3 participants 6 participants 4 participants 31 participants 7 participants 3 participants 4 participants 7 participants 7 participants 3 participants 4 participants 2 participants 102 participants
Female
3
  60.0%
0
   0.0%
0
   0.0%
5
  71.4%
2
  28.6%
2
  66.7%
2
  33.3%
2
  50.0%
13
  41.9%
3
  42.9%
1
  33.3%
2
  50.0%
3
  42.9%
2
  28.6%
0
   0.0%
2
  50.0%
2
 100.0%
44
  43.1%
Male
2
  40.0%
1
 100.0%
1
 100.0%
2
  28.6%
5
  71.4%
1
  33.3%
4
  66.7%
2
  50.0%
18
  58.1%
4
  57.1%
2
  66.7%
2
  50.0%
4
  57.1%
5
  71.4%
3
 100.0%
2
  50.0%
0
   0.0%
58
  56.9%
1.Primary Outcome
Title Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle (28 Days)
Hide Description DLT was defined as any of the following hematologic or non-hematologic events which were attributable to the combination study drug and occurring in the first 28-day cycle: 1) Grade 4 neutropenia lasting greater than (>)7 days; 2) Febrile neutropenia (defined as neutropenia greater than or equal to [≥]Grade 3 and a body temperature ≥38.5°C); 3) Grade ≥3 neutropenic infection; 4) Grade 3 thrombocytopenia with bleeding; 5) Grade 4 thrombocytopenia; 6) Grade ≥3 toxicities; 7) Persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses during the first cycle; 8) Persistent, intolerable toxicities which resulted in delay of start of Cycle 2 by more than 2 weeks of scheduled day; 9) Persistent Grade 3 QTc prolongation (QTc >500 msec) after correction of any reversible causes.
Time Frame Baseline up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment and who did not have a major pre-specified treatment deviation in the first cycle of treatment in Stage 1.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 5 3 6 4 7 3 4 7 7 3 3 1
Measure Type: Number
Unit of Measure: percentage of participants
40.0 0 100 14.3 40.0 0 0 50.0 14.3 0 0 14.3 14.3 0 0 0
2.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Measure Type: Number
Unit of Measure: participants
AEs 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
SAEs 2 1 1 2 5 0 0 2 5 3 1 2 4 1 0 1 0
3.Secondary Outcome
Title Number of Participants With Treatment-Emergent AEs (TEAEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs were graded by the NCI CTCAE (Version 4.0).
Time Frame Baseline up to End of Treatment (EOT) (within 28 days after last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Measure Type: Number
Unit of Measure: participants
Any AEs, Grade 1 0 0 0 0 0 0 2 0 7 0 0 0 0 0 0 1 1
Any AEs, Grade 2 2 0 0 5 2 3 4 1 10 2 2 2 3 2 1 3 0
Any AEs, Grade 3 2 1 1 2 5 0 0 2 10 3 1 1 2 4 2 0 1
Any AEs, Grade 4 1 0 0 0 0 0 0 1 4 1 0 1 0 1 0 0 0
Any AEs, Grade 5 0 0 0 0 0 0 0 0 0 1 0 0 2 0 0 0 0
Any AEs, Missing or Unknown 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Any AEs, Total 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
4.Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Hematology)
Hide Description Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 hematological test abnormalities. Hematological tests included platelet count, hemoglobin, and white blood cell (WBC) count with 5- part differential.
Time Frame Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Measure Type: Number
Unit of Measure: participant
Anemia 5 1 1 5 6 3 6 4 31 6 3 3 7 5 3 3 2
Hemoglobin Increased 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Lymphocyte Count Increased 0 0 0 0 0 0 0 0 1 1 1 0 1 1 0 0 0
Lymphopenia 5 1 1 7 7 3 5 3 22 5 1 1 6 6 3 1 1
Absolute Neutrophils 1 0 0 3 3 0 2 3 18 0 0 0 0 1 0 1 1
Platelets 3 0 0 4 2 1 1 3 10 0 0 2 1 3 1 1 1
White Blood Cells 3 0 0 5 3 3 3 4 22 1 0 0 2 0 1 1 1
5.Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Coagulation)
Hide Description Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 coagulation test abnormalities. Coagulation tests included partial thromboplastin time (PTT) and prothrombin time (PT) international normalized ratio (INR).
Time Frame Baseline, Days 1 and 15 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment. N=number of evaluable participants for each parameter.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Measure Type: Number
Unit of Measure: participant
PTT (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2) 2 0 0 2 5 2 0 2 21 2 3 2 2 5 0 3 2
PT INR (N=5,1,1,7,7,3,6,4,30,7,3,4,7,7,3,4,2) 1 0 1 2 5 0 1 2 13 0 1 1 3 2 1 2 0
6.Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Chemistry)
Hide Description Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 chemistry test abnormalities. Chemistry tests included aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]), serum creatinine, total bilirubin, direct/indirect bilirubin, alkaline phosphatase, chloride, uric acid, phosphorus, calcium, magnesium, potassium, sodium, blood urea nitrogen (BUN) or urea, total protein, albumin, glucose, and insulin.
Time Frame Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Measure Type: Number
Unit of Measure: participant
ALT 3 0 1 2 3 0 3 3 13 3 1 2 5 4 3 1 2
Alkaline phosphatase 3 1 1 5 6 1 3 2 22 4 3 4 6 6 3 4 2
AST 4 0 1 3 5 0 3 2 16 4 2 3 5 6 3 3 2
Total bilirubin 0 0 1 2 2 0 1 1 3 2 0 2 1 4 1 1 0
creatinine 5 1 0 5 6 3 5 3 21 5 2 3 5 2 3 4 2
hypercalcemia 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 1 0
hyperglycemia 5 1 1 6 6 3 5 3 25 5 2 3 7 7 2 4 2
hyperkalemia 1 0 0 2 1 0 1 1 2 1 1 0 1 2 0 0 0
hypermagnesemia 0 0 0 0 0 0 0 1 2 2 0 0 2 1 0 0 1
hypernatremia 1 0 0 0 1 0 0 1 2 0 0 0 0 0 0 1 0
hypoalbuminemia 3 1 1 3 6 0 3 3 18 3 2 4 6 6 3 2 2
hypocalcemia 3 0 1 4 4 1 0 4 13 2 2 3 1 4 1 1 2
hypoglycemia 0 0 0 0 1 0 1 0 3 1 1 1 0 2 1 0 0
hypokalemia 2 1 1 2 3 0 0 3 14 3 1 2 3 4 0 2 1
hypomagnesemia 2 0 0 3 4 2 2 1 10 2 1 2 0 2 1 2 1
hyponatremia 1 1 0 4 3 0 1 3 14 2 2 2 4 3 1 1 1
hypophosphatemia 4 1 0 2 5 0 2 1 8 1 1 1 3 3 0 1 0
7.Secondary Outcome
Title Number of Participants With Laboratory Test Abnormalities (Urinalysis)
Hide Description Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 urinalysis test abnormalities for urine protein.
Time Frame Baseline, Days 1 and 15 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment. Number of participants analyzed=number of evaluable participants for each laboratory parameter.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 31 7 3 4 6 7 3 4 2
Measure Type: Number
Unit of Measure: participant
2 1 1 6 4 1 3 1 15 3 0 2 5 4 1 2 0
8.Secondary Outcome
Title Number of Participants With Vital Signs Values Meeting Prespecified Criteria
Hide Description Number of participants with vital signs values meeting prespecified criteria. Criteria defined as: 1) absolute systolic blood pressue (SBP) less than or equal to (<=) 100 millimeter of mercury (mmHg); 2) absolute SBP greater than or equal to (>=) 160 mmHg, 3) SBP maximum increase of >=20 mmHg from baseline; 4) SBP maximum increase of >=40 mmHg from baseline; 5) SBP maximum increase of >=60 mmHg from baseline; 6) absolute diastolic blood pressure (DBP) <=60 mmHg; 7) absolute DBP >=100 mmHg; 8) DBP maximum increase of >=10 mmHg from baseline; 9) DBP maximum increase of >=20 mmHg from baseline; 10) DBP maximum increase of >=30 mmHg from baseline; 11) absolute heart rate (HR) <50 beats per minute (bpm); 12) absolute HR >120 bpm.
Time Frame Baseline, Days 1, 15, and 23 of Cycle 1, Days 1 and 15 of Cycle 2, Day 1 of Cycle 3 and subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment. N=number of participants evaluated against criteria.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Measure Type: Number
Unit of Measure: participants
Criterion 1 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2) 1 0 0 4 3 0 1 1 9 2 2 3 1 2 0 1 2
Criterion 2 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2) 1 0 0 0 0 1 0 0 4 2 0 0 3 0 0 1 0
Criterion 3 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1) 1 0 0 0 0 0 0 1 7 3 1 1 3 0 0 2 0
Criterion 4 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1) 0 0 0 0 0 0 0 0 1 2 0 0 1 0 0 1 0
Criterion 5 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1) 0 0 0 0 0 0 0 0 1 0 0 0 1 0 0 1 0
Criterion 6 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2) 0 0 0 3 3 1 2 1 14 1 2 1 2 3 1 1 1
Criterion 7 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2) 0 0 0 1 0 0 0 0 3 1 0 0 0 0 0 0 0
Criterion 8 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1) 3 0 1 4 1 1 0 3 10 1 1 2 3 0 1 3 1
Criterion 9 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1) 0 0 1 1 0 1 0 0 1 1 1 0 1 0 0 0 0
Criterion10 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1) 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0
Criterion11 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2) 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0
Criterion12 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2) 0 1 0 0 0 0 1 0 0 1 0 0 1 0 0 0 0
9.Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C
Hide Description [Not Specified]
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the pharmacokinetic (PK) parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Hide Arm/Group Description:
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Overall Number of Participants Analyzed 2 6 4 30
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram (ng)/milliliter (mL)
Cycle 1 Day 2 (N=2, 6, 4, 30)
NA [1] 
(NA%)
3404
(82%)
4759
(25%)
5221
(61%)
Cycle 1 Day 16 (N=3, 6, 4, 28)
2201
(16%)
2814
(50%)
4656
(32%)
5728
(56%)
[1]
For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP. Individual values of these 2 participants were 1640 and 3050 ng/mL, respectively.
10.Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Hide Description [Not Specified]
Time Frame Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 7 3 4 7 6 3 4 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 0 Day -14 (N=7, 3, 4, 7, 6, 3, 4, 2)
3625
(62%)
5937
(32%)
11170
(16%)
8476
(32%)
8586
(36%)
6279
(70%)
7239
(39%)
NA [1] 
(NA%)
Cycle 1 Day 15 (N=5, 3, 4, 6, 5, 1, 4, 1)
8621
(18%)
6153
(34%)
12440
(32%)
8717
(50%)
8913
(54%)
9280 [2] 
(NA%)
7989
(45%)
15400 [2] 
(NA%)
[1]
For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP. Individual values of these 2 participants were 9250 and 15200 ng/mL, respectively.
[2]
Individual value is reported. For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP.
11.Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PD-0325901 on Cycle 0 Day -1 and Cycle 1 Day 1 for Arm D
Hide Description [Not Specified]
Time Frame Cycle 0 Day -1 and Cycle 1 Day 1: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 7 3 3 7 7 3 3 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 0 Day -1 (N=7, 3, 3, 7, 7, 3, 3, 2)
85.28
(27%)
63.80
(14%)
87.99
(51%)
180.6
(28%)
191.9
(44%)
115.8
(70%)
231.3
(69%)
NA [1] 
(NA%)
Cycle 1 Day 1 (N=5, 3, 3, 6, 6, 3, 4, 2)
91.69
(31%)
74.23
(43%)
64.99
(56%)
138.7
(23%)
183.6
(29%)
114.6
(50%)
211.9
(44%)
NA [2] 
(NA%)
[1]
For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP. Individual values of these 2 participants were 204 and 372 ng/mL, respectively.
[2]
For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP. Individual values of these 2 participants were 247 and 428 ng/mL, respectively.
12.Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PD-0325901 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 0 Day -7 (N=5, 1, 1)
304.9
(49%)
280 [1] 
(NA%)
101 [1] 
(NA%)
Cycle 1 Day 12 (N=4, 1, 1)
341.9
(21%)
690 [1] 
(NA%)
182 [1] 
(NA%)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
13.Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 0 Day -7 (N=5, 1, 1)
38.02
(28%)
59.8 [1] 
(NA%)
48.7 [1] 
(NA%)
Cycle 1 Day 12 (N=4, 1, 1)
52.02
(13%)
21.2 [1] 
(NA%)
64.7 [1] 
(NA%)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
14.Secondary Outcome
Title Maximum Plasma Concentrations (Cmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose) and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6 8 and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 0 Day -7 (N=7, 7) 41.44  (8.1201) 68.41  (31.818)
Cycle 1 Day 12 (N=7, 5) 46.81  (19.381) 87.30  (37.647)
15.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C
Hide Description [Not Specified]
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Hide Arm/Group Description:
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Overall Number of Participants Analyzed 2 6 4 30
Median (Full Range)
Unit of Measure: hour (hr)
Cycle 1 Day 2 (N=2, 6, 4, 30)
1.30
(1.00 to 1.60)
1.02
(0.500 to 1.67)
0.992
(0.500 to 1.00)
0.500
(0.467 to 1.07)
Cycle 1 Day 16 (N=3, 6, 4, 28)
1.00
(1.00 to 1.08)
0.992
(0.583 to 1.05)
0.734
(0.500 to 1.00)
0.525
(0.333 to 2.92)
16.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Hide Description [Not Specified]
Time Frame Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 7 3 4 7 6 3 4 2
Median (Full Range)
Unit of Measure: hr
Cycle 0 Day -14 (N=7, 3, 4, 7, 6, 3, 4, 2)
0.500
(0.500 to 1.00)
0.500
(0.500 to 0.983)
0.500
(0.500 to 0.500)
0.500
(0.500 to 3.22)
0.509
(0.500 to 0.583)
1.00
(0.500 to 3.08)
0.500
(0.500 to 0.600)
0.500
(0.500 to 0.500)
Cycle 1 Day 15 (N=5, 3, 4, 6, 5, 1, 4, 1)
0.500
(0.500 to 0.500)
0.500
(0.500 to 1.00)
0.500
(0.500 to 0.517)
0.509
(0.500 to 0.567)
0.517
(0.500 to 0.583)
0.667
(0.667 to 0.667)
0.500
(0.500 to 3.92)
0.500
(0.500 to 0.500)
17.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PD-0325901 on Cycle 0 Day -1 and Cycle 1 Day 1 for Arm D
Hide Description [Not Specified]
Time Frame Cycle 0 Day -1 and Cycle 1 Day 1: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 7 3 3 7 7 3 3 2
Median (Full Range)
Unit of Measure: hr
Cycle 0 Day -1 (N=7, 3, 3, 7, 7, 3, 3, 2)
1.00
(1.00 to 6.02)
2.00
(2.00 to 3.00)
1.03
(1.00 to 2.33)
1.97
(0.917 to 4.00)
1.07
(1.00 to 2.00)
1.00
(0.333 to 4.00)
2.00
(1.00 to 4.00)
2.50
(1.00 to 4.00)
Cycle 1 Day 1 (N=5, 3, 3, 6, 6, 3, 4, 2)
1.00
(1.00 to 2.00)
2.00
(1.00 to 4.00)
1.00
(1.00 to 4.00)
2.00
(1.00 to 4.00)
1.00
(1.00 to 2.02)
2.00
(2.00 to 4.05)
1.50
(1.00 to 6.00)
1.00
(1.00 to 1.00)
18.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PD-0325901 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12: Pre-dose and 1, 2, 4, 6 and 8 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Median (Full Range)
Unit of Measure: hr
Cycle 0 Day -7 (N=5, 1, 1)
1.00
(1.00 to 4.00)
2.00
(2.00 to 2.00)
1.92
(1.92 to 1.92)
Cycle 1 Day 12 (N=4, 1, 1)
1.00
(1.00 to 1.02)
1.00
(1.00 to 1.00)
4.00
(4.00 to 4.00)
19.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Median (Full Range)
Unit of Measure: hr
Cycle 0 Day -7 (N=5, 1, 1)
1.00
(1.00 to 6.00)
1.00
(1.00 to 1.00)
1.90
(1.90 to 1.90)
Cycle 1 Day 12 (N=4, 1, 1)
2.00
(1.02 to 2.00)
0.00
(0.00 to 0.00)
2.00
(2.00 to 2.00)
20.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose) and 1, 2, 4, 6, 8, 24, and 72 hours post-dose. Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6 8 and 24 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Overall Number of Participants Analyzed 7 7
Median (Full Range)
Unit of Measure: hr
Cycle 0 Day -7 (N=7, 7)
2
(1 to 8)
1.07
(1 to 4.13)
Cycle 1 Day 12 (N=7, 5)
2
(1 to 4)
2.03
(1.02 to 6)
21.Secondary Outcome
Title Terminal Elimination Half Life (t½) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C
Hide Description [Not Specified]
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Hide Arm/Group Description:
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Overall Number of Participants Analyzed 1 5 3 25
Mean (Standard Deviation)
Unit of Measure: hr
Cycle 1 Day 2 (N=1, 5, 3, 25) 24.5 [1]   (NA) 32.14  (1.3334) 29.23  (7.1066) 32.16  (4.5154)
Cycle 1 Day 16 (N=1, 5, 3, 20) 33.3 [1]   (NA) 37.98  (5.5603) 34.50  (8.4256) 35.10  (3.3067)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
22.Secondary Outcome
Title Terminal Elimination Half Life (t½) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Hide Description [Not Specified]
Time Frame Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 3 3 6 6 3 4 2
Mean (Standard Deviation)
Unit of Measure: hr
Cycle 0 Day -14 (N=5, 3, 3, 6, 6, 3, 4, 2) 24.62  (3.2306) 27.37  (6.4748) 30.77  (6.4933) 25.85  (4.1530) 29.35  (5.5121) 29.63  (3.7072) 27.05  (4.6651) NA [1]   (NA)
Cycle 1 Day 15 (N=3, 3, 4, 6, 3, 1, 3, 1) 35.90  (4.8816) 39.30  (10.678) 41.25  (6.2303) 34.43  (8.5383) 40.20  (5.8643) 37.0 [2]   (NA) 33.30  (0.96437) 37.0 [2]   (NA)
[1]
For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP. Individual values of these 2 participants were 24.6 and 24.8 hr, respectively.
[2]
Individual value is reported. For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP.
23.Secondary Outcome
Title Terminal Elimination Half Life (t½) for PD-0325901 on Cycle 0 Day -7 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the pharmacokinetic (PK) parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Mean (Standard Deviation)
Unit of Measure: hr
13.92  (4.2260) 18.3 [1]   (NA) 25.7 [1]   (NA)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
24.Secondary Outcome
Title Terminal Elimination Half Life (t1/2) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Mean (Standard Deviation)
Unit of Measure: hr
Cycle 0 Day -7 (N=5, 1, 1) 9.374  (1.3243) 12.4 [1]   (NA) 11.5 [1]   (NA)
Cycle 1 Day 12 (N=4, 0, 0) 8.968  (1.5366) NA [2]   (NA) NA [2]   (NA)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
[2]
N = 0.
25.Secondary Outcome
Title Terminal Elimination Half Life (t1/2) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: hr
Cycle 0 Day -7 (N=6, 7) 13.13  (2.2879) 13.06  (2.6589)
Cycle 1 Day 12 (N=3, 1) 8.597  (1.2726) 8.97 [1]   (NA)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
26.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05212384 on Cycle 1 Day 2 and Cycle 1 Day 16 for Arm C
Hide Description [Not Specified]
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Hide Arm/Group Description:
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Overall Number of Participants Analyzed 3 6 4 31
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1 Day 2 (N=2, 6, 4, 30)
NA [1] 
(NA%)
7487
(41%)
10530
(44%)
9485
(43%)
Cycle 1 Day 16 (N=3, 6, 4, 28)
8819
(71%)
8243
(25%)
11170
(53%)
10890
(38%)
[1]
For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP. Individual values of these 2 participants were 7410 and 10500 ng*hr/mL, respectively.
27.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Hide Description [Not Specified]
Time Frame Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 7 3 4 7 7 3 4 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 0 Day -14 (N=7, 3, 4, 7, 6, 3, 4, 2)
7627
(46%)
10250
(21%)
14850
(31%)
12590
(27%)
14280
(24%)
13840
(47%)
9619
(22%)
NA [1] 
(NA%)
Cycle 1 Day 15 (N=5, 3, 4, 6, 5, 1, 4, 1)
12070
(36%)
12130
(1%)
19970
(25%)
13390
(21%)
21170
(36%)
15200 [2] 
(NA%)
12610
(25%)
20800 [2] 
(NA%)
[1]
For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP. Individual values of these 2 participants were 14900 and 18800 ng*hr/mL, respectively.
[2]
Individual value is reported. For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP.
28.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PD-0325901 on Cycle 0 Day -7 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
1479
(23%)
2030 [1] 
(NA%)
941 [1] 
(NA%)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
29.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-04691502 on Cycle 0 Day -7 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
474.5
(29%)
933 [1] 
(NA%)
688 [1] 
(NA%)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
30.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-04691502 on Cycle 0 Day -7 for Arm B
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Overall Number of Participants Analyzed 7 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
588.4
(49%)
1001
(35%)
31.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-05212384 on Cycle 1 Day 2 and Cycle 1 Day 16 for Arm C
Hide Description [Not Specified]
Time Frame Cycle 1 Day 2 and Cycle 1 Day 16: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2)
Hide Arm/Group Description:
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Overall Number of Participants Analyzed 3 6 4 31
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1 Day 2 (N=1, 5, 3, 25)
7540 [1] 
(NA%)
7968
(41%)
9277
(48%)
10070
(42%)
Cycle 1 Day 16 (N=1, 5, 3, 20)
5870 [1] 
(NA%)
8627
(26%)
9174
(17%)
10610
(37%)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
32.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D
Hide Description [Not Specified]
Time Frame Cycle 0 Day -14 and Cycle 1 Day 15: Pre-dose and 0.5, 1, 2, 4, 6, 8, 24, 72, and 120 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.
Arm/Group Title PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 7 3 4 7 7 3 4 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 0 Day -14 (N=5, 3, 3, 6, 6, 3, 4, 2)
6353
(40%)
10460
(20%)
14880
(39%)
12600
(29%)
14620
(23%)
14230
(46%)
9766
(22%)
NA [1] 
(NA%)
Cycle 1 Day 15 (N=3, 3, 4, 6, 3, 1, 3, 1)
10430
(33%)
12460
(2%)
20440
(26%)
13770
(20%)
23730
(39%)
15500 [2] 
(NA%)
13320
(27%)
21300 [2] 
(NA%)
[1]
For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP. Individual values of these 2 participants were 15100 and 19100 ng*hr/mL, respectively.
[2]
Individual value is reported. For arms with <3 participants with reportable values, data summary statistics were not calculated per standard practice and as specified in the SAP.
33.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PD-0325901 on Cycle 0 Day -7 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7: Pre-dose and 1, 2, 4, 6, 8, 24, and 72 hours post-dose.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
1599
(26%)
2140 [1] 
(NA%)
1060 [1] 
(NA%)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
34.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-04691502 on Cycle 0 Day -7 for Arm A
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.
Hide Outcome Measure Data
Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
523.9
(21%)
950 [1] 
(NA%)
697 [1] 
(NA%)
[1]
Individual value is reported. Summary statistics are not presented if fewer than 3 subjects have reportable parameter values.
35.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-04691502 on Cycle 0 Day -7 for Arm B
Hide Description [Not Specified]
Time Frame Cycle 0 Day -7 at 0 hours (pre-dose), 1, 2, 4, 6, 8, 24, and 72 hours, and at Cycle 1 Day 12 at 0 hours (pre-dose), 1, 2, 4, 6, 8, and 24 hours.
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Hide Analysis Population Description
Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Overall Number of Participants Analyzed 6 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
705.0
(41%)
1028
(36%)
36.Secondary Outcome
Title Number of Participants With Increase From Baseline in QT Interval
Hide Description Electrocardiogram (ECG) measurements (an average of the triplicate measurements) were used for the statistical analysis and all data presentations. QT intervals were corrected for heart rate (QTc) using Bazett’s Formula (QTcB) and Fridericia’s Formula (QTcF) .
Time Frame Baseline, Cycle 1 Day 2 for Arms C and D, Cycle 1 Day 15 for Arm D, and Cycle 1 Day 16 for Arm C, Day 2 in Arm C and Day 1 in Arm D for subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)
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Hide Analysis Population Description
All participants enrolled in the study having at least one ECG assessment after receiving study drug for the respective arm.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 30 7 3 3 7 5 3 4 2
Measure Type: Number
Unit of Measure: participants
Maximum QTcB Interval Increase <30msec 4 0 1 7 7 2 5 4 28 7 2 2 6 4 3 3 2
MaximumQTcB Interval Increase >=30to<60msec 1 1 0 0 0 1 1 0 2 0 1 1 1 1 0 1 0
Maximum QTcB Interval Increase >=60 msec 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Maximum QTcF Interval Increase <30 msec 5 0 1 7 5 2 5 3 24 6 3 2 6 5 3 4 2
MaximumQTcF Interval Increase >=30 to<60msec 0 1 0 0 2 1 1 1 6 1 0 1 1 0 0 0 0
Maximum QTcF Interval Increase >=60 msec 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
37.Secondary Outcome
Title Number of Participants With Maximum Post-dose QT Interval Corrected
Hide Description Electrocardiogram (ECG) measurements (an average of the triplicate measurements) were used for the statistical analysis and all data presentations. QT intervals were corrected for heart rate (QTc) using Bazett’s Formula (QTcB) and Fridericia’s Formula (QTcF).
Time Frame Baseline, Cycle 1 Day 2 for Arms C and D, Cycle 1 Day 15 for Arm D, and Cycle 1 Day 16 for Arm C, Day 2 in Arm C and Day 1 in Arm D for subsequent cycles, up to End of Treatment (within 28 days of last treatment administration)
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Hide Analysis Population Description
All participants enrolled in the study having at least one ECG assessment after receiving study drug for the respective arm.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 7 3 6 4 31 7 3 4 7 7 3 4 2
Measure Type: Number
Unit of Measure: participants
Maximum QTcB Interval <450 msec 2 0 1 4 3 2 4 1 22 2 3 3 2 4 3 2 1
Maximum QTcB Interval 450 to <=480 msec 3 0 0 3 4 1 2 3 5 5 0 1 5 1 0 1 0
Maximum QTcB Interval >480 to <=500 msec 0 0 0 0 0 0 0 0 2 0 0 0 0 2 0 0 1
Maximum QTcB Interval >500 msec 0 1 0 0 0 0 0 0 2 0 0 0 0 0 0 1 0
Maximum QTcF Interval <450 msec 4 0 1 7 3 3 6 2 24 6 3 4 6 5 3 2 1
Maximum QTcF Interval 450 to <=480 msec 1 0 0 0 4 0 0 2 5 1 0 0 1 2 0 2 0
Maximum QTcF Interval >480 to <=500 msec 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 1
Maximum QTcF Interval >500 msec 0 1 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0
38.Secondary Outcome
Title Percentage of Participants With Complete Response (CR) or Partial Response (PR)
Hide Description CR was defined as the disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 mm). PR was defined as at least a 30% decrease in the sum of the longest diameters of the targeted lesions.
Time Frame Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until progression of disease was documented.
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Hide Analysis Population Description
All participants who started treatment on the assigned arm and had an adequate baseline tumor assessment.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 7 6 3 6 4 30 7 3 3 7 7 3 4 2
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0 0 0 33.3 0 0 3.3 0 33.3 0 28.6 14.3 0 0 0
39.Secondary Outcome
Title Progression-Free Survival (PFS) (Stage 2)
Hide Description Progression-free survival (PFS) was the time from first dose to date of first documentation of progression or death due to any cause.
Time Frame Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until progression of disease was documented.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who started treatment on the assigned arm and had an adequate baseline tumor assessment.
Arm/Group Title PF-05212384+Irinotecan: Arm C2 (Stage 2)
Hide Arm/Group Description:
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Overall Number of Participants Analyzed 30
Median (95% Confidence Interval)
Unit of Measure: months
2.8
(1.7 to 3.7)
40.Secondary Outcome
Title Ratio to Baseline in Serum Glucose Level at End of Treatment for Arm B, Arm C, and Arm D
Hide Description [Not Specified]
Time Frame Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment and had baseline and on treatment serum biomarker samples (glucose, insulin, or other serum biomarkers) successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 5 2 5 3 25 5 3 2 6 5 3 4 1
Mean (Standard Deviation)
Unit of Measure: ratio
0.974  (0.0864) 1.015  (0.1935) NA [1]   (NA) 1.011  (0.1165) NA [2]   (NA) 1.111  (0.2895) 1.212  (0.3284) NA [3]   (NA) NA [4]   (NA) 0.966  (0.1904) 1.13  (0.3886) NA [5]   (NA) NA [6]   (NA) NA [7]   (NA)
[1]
Arm C1 for Stage 1 had 2 participants with data at End of treatment and were not summarized. The individual values were 1.305 and 1.293.
[2]
Arm C3 for Stage 1 had 3 participants with data at End of treatment and were not summarized. The individual values were 0.64, 1.262, and 1.093.
[3]
Arm D0A for Stage 1 had 3 participants with data at End of treatment and were not summarized. The individual values were 0.708 , 0.973 and 1.024.
[4]
Arm D0B for Stage 1 had 2 participants with data at End of treatment and were not summarized. The individual values were 0.956 and 1.104.
[5]
Arm D1B for Stage 1 had 3 participants with data at End of treatment and were not summarized. The individual values were 1.641,1.198 and 0.947.
[6]
Arm D2 for Stage 1 had 4 participants with data at End of treatment and were not summarized. The individual values were 0.93, 0.74, 1.113 and 0.817.
[7]
Arm D2A for Stage 1 had 1 participants with data at End of treatment and were not summarized. The individual values was 0.783.
41.Secondary Outcome
Title Ratio to Baseline in Serum Insulin Level at End of Treatment for Arm B, Arm C, and Arm D
Hide Description [Not Specified]
Time Frame Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment and had baseline and on treatment serum biomarker samples (glucose, insulin, or other serum biomarkers) successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 4 6 2 5 3 22 4 3 1 5 4 3 4 1
Mean (Standard Deviation)
Unit of Measure: ratio
NA [1]   (NA) 1.628  (1.888) NA [2]   (NA) 2.178  (2.3194) NA [3]   (NA) 1.699  (2.0031) NA [4]   (NA) NA [5]   (NA) NA [6]   (NA) 2.233  (2.3617) NA [7]   (NA) NA [8]   (NA) NA [9]   (NA) NA [10]   (NA)
[1]
Arm B1 for Stage 1 had 4 participants with data at End of treatment and were not summarized. The individual values were 0.412, 2.2, 1, 0.973.
[2]
Arm C1 for Stage 1 had 2 participants with data at End of treatment and were not summarized. The individual values were 1.528 and 1.14.
[3]
Arm C3 for Stage 1 had 3 participants with data at End of treatment and were not summarized. The individual values were 0.244, 0.769, 0.552.
[4]
Arm D0 for Stage 1 had 4 participants with data at End of treatment and were not summarized. The individual values were 0.833, 5.143, 0.979, 0.744.
[5]
Arm D0A for Stage 1 had 3 participants with data at End of treatment and were not summarized. The individual values were 0.374, 0.905, 0.736.
[6]
Arm D0B for Stage 1 had 1 participant with data at End of treatment and was not summarized. The individual value was 1.434.
[7]
Arm D1A for Stage 1 had 4 participants with data at End of treatment and were not summarized. The individual values were2.026, 0.665, 0.32, 4.404.
[8]
Arm D1B for Stage 1 had 3 participants with data at End of treatment and were not summarized. The individual values were 2.116, 1.187, 1.172.
[9]
Arm D2 for Stage 1 had 4 participants with data at End of treatment and were not summarized. The individual values were 0.403, 0.281, 3.293, 3.776.
[10]
Arm D2A for Stage 1 had 1 participant with data at End of treatment and was not summarized. The individual value was 0.083.
42.Secondary Outcome
Title Ratio to Baseline in Serum Glucose Level at Cycle 2 Day 16 for Arm A
Hide Description [Not Specified]
Time Frame Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment and had baseline and on treatment serum biomarker samples (glucose, insulin, or other serum biomarkers) successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 0
Mean (Standard Deviation)
Unit of Measure: ratio
0.965  (0.2697) NA [1]   (NA)
[1]
Arm A2 for Stage 1 had only 1 participant with data at Cycle 2 Day 16 and was not summarized. The individual value for the 1 participant was 1.035.
43.Secondary Outcome
Title Ratio to Baseline in Serum Insulin Level at Cycle 2 Day 16 for Arm A
Hide Description [Not Specified]
Time Frame Baseline, Cycle 1 Days 2, 15, 22, and 23, Cycle 2 Days 1 and 16, Day 1 in Cycle 3 and subsequent cycles, and EOT (within 28 days after last treatment administration)
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment and had baseline and on treatment serum biomarker samples (glucose, insulin, or other serum biomarkers) successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 0
Mean (Standard Deviation)
Unit of Measure: ratio
0.652  (0.3622) NA [1]   (NA)
[1]
Arm A2 for Stage 1 had only 1 participant with data at Cycle 2 Day 16 and was not summarized. The individual value for the 1 participant was 0.972.
44.Secondary Outcome
Title Number of Participants With Expression of Genes Relating to Phosphatidylinositol 3 Kinase (PI3K), Mitogen Activated Protein Kinase (MAPK) and/or Wingless-Type Mouse Mammary Tumor Virus Integration Site Family Member (Wnt) Pathway Signaling
Hide Description Number of participants with expression of genes relating to PI3K, MAPK and/or Wnt pathway signaling (kirsten rat sarcoma 2 viral oncogene homolog [KRAS] and PTEN protein). Biopsies were obtained at baseline and Cycle 1 Day 23. Biomarker evaluation was performed on these biopsies.
Time Frame Baseline and Cycle 1 Day 23.
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled participants who started treatment and had baseline tumor tissues successfully analyzed for at least one of the biomarkers.
Arm/Group Title PF-04691502+PF-0325901: Arm A1 (Stage1) PF-04691502+PF 0325901: Arm A2 (Stage1) PF-04691502+PF 0325901: Arm A4 (Stage1) PF-04691502+Irinotecan: Arm B1 (Stage 1) PF-04691502+Irinotecan: Arm B2 (Stage 1) PF-05212384+Irinotecan: Arm C1 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 1) PF-05212384+Irinotecan: Arm C3 (Stage 1) PF-05212384+Irinotecan: Arm C2 (Stage 2) PF-05212384+ PD-0325901: Arm D0 (Stage 1) PF-05212384+ PD-0325901: Arm D0A (Stage 1) PF-05212384+ PD-0325901: Arm D0B (Stage 1) PF-05212384+ PD-0325901: Arm D1 (Stage 1) PF-05212384+ PD-0325901: Arm D1A (Stage 1) PF-05212384+PD-0325901: Arm D1B (Stage 1) PF-05212384+PD-0325901: Arm D2 (Stage 1) PF-05212384+ PD-0325901: Arm D2A (Stage 1)
Hide Arm/Group Description:
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly.
Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.
Overall Number of Participants Analyzed 5 1 1 6 7 3 5 4 24 4 2 3 6 7 3 2 1
Measure Type: Number
Unit of Measure: participants
KRAS mutation 4 1 1 0 3 0 2 1 10 2 1 2 4 6 2 1 1
PTEN tumor manual score 4 1 1 5 6 3 5 4 24 4 2 3 6 7 2 2 1
PTEN stroma manual score 4 1 1 5 6 3 4 4 24 4 2 3 6 7 2 2 1
45.Secondary Outcome
Title Duration of Response (Stage 2)
Hide Description Duration of response was to be calculated for participants with an objective response. Duration of PR or CR was the time from start date (date of first documentation of PR or CR) to date of first documentation of objective progression or death. CR: disappearance of a target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.
Time Frame Baseline, every 8 weeks in Cycle 3 and subsequent cycles, until until progression of disease was documented.
Hide Outcome Measure Data