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ATX Study:A Study of Avastin (Bevacizumab), Tarceva (Erlotinib) and Xeloda (Capecitabine) in Patients With Locally Advanced and/or Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT00925769
Recruitment Status : Completed
First Posted : June 22, 2009
Results First Posted : August 7, 2015
Last Update Posted : August 7, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pancreatic Cancer
Interventions Drug: bevacizumab [Avastin]
Drug: capecitabine [Xeloda]
Drug: erlotinib [Tarceva]
Enrollment 32
Recruitment Details  
Pre-assignment Details Thirty two (32) participants were included however, 2 participants discontinued before reaching the end of the evaluation period of 3 cycles of the complete study regimen (of all 3 drugs) at the recommended dose due to progressive disease.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description Participants were administered oral 100 milligrams (mg) of erlotinib (ERL) tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 milligrams per kilogram (mg/kg) of bevacizumab (BEV) intravenous (IV) infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 milligrams per square meter (mg/m^2) of capecitabine (CAP) tablet twice daily (BID) within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 6 6 6 6 3 3
Completed 0 0 0 0 0 0
Not Completed 6 6 6 6 3 3
Reason Not Completed
Major toxicity             1             0             1             1             0             0
Disease progression             4             5             3             4             2             3
Death             0             0             1             0             0             0
Physician Decision             1             0             0             0             0             0
Missing documentation             0             1             0             0             0             0
End of study visit not done             0             0             1             0             0             0
Participant is unable to swallow drug             0             0             0             1             0             0
Adverse Event             0             0             0             0             1             0
Arm/Group Title Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
Hide Arm/Group Description Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (Dose levels [DL]-1, 2, 3, 4, 5 and 6) were administered either oral 100 mg or 150 mg of erlotinib tablet daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
Per-protocol population: All participants who received at least 1 evaluation period of 3 cycles of the complete study regimen (of all 3 drugs) at the recommended dose unless withdrawn from therapy earlier because of toxicity.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
63.9  (8.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
15
  50.0%
Male
15
  50.0%
1.Primary Outcome
Title Part 1: Maximum Tolerated Dose (MTD) of Capecitabine
Hide Description MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33 percent (%) of participants of the same quality category. DLT was defined as any greater than or equal to (>=) Grade (G) 3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to adverse events (AEs).
Time Frame Up to Week 6 (Cycle 1-3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population.
Arm/Group Title Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
Hide Arm/Group Description:
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: mg/m^2 BID
900
2.Primary Outcome
Title Part 1: MTD of Erlotinib
Hide Description MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs.
Time Frame Up to Week 6 (Cycle 1-3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population.
Arm/Group Title Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
Hide Arm/Group Description:
Dose-escalation was performed using a substance related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DL-1, 2, 3, 4, 5 and 6) were administered with either 100 mg or 150 mg of erlotinib daily orally, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: mg/day
NA [1] 
[1]
DLTs were not observed for the maximum planned dose of erlotinib (150 mg/day) in the study; therefore, MTD was not defined for erlotinib.
3.Primary Outcome
Title Part 1: MTD of Bevacizumab
Hide Description MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs.
Time Frame Up to Week 6 (Cycle 1-3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population.
Arm/Group Title Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
Hide Arm/Group Description:
Dose-escalation was performed using a substance related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DL-1, 2, 3, 4, 5 and 6) were administered with either 100 mg or 150 mg of erlotinib daily orally, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: mg/kg once every 2 weeks (Q2W)
NA [1] 
[1]
DLTs were not observed for the maximum planned dose of bevacizumab (10 mg/kg once Q2W) in the study; therefore, MTD was not defined for capecitabine.
4.Primary Outcome
Title Part 1: Preliminary Recommended Dose (PRD) of Capecitabine for Part 2
Hide Description Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in dose limiting toxicity (DLT) in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
Time Frame Up to Week 6 (Cycle 1-3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population.
Arm/Group Title Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
Hide Arm/Group Description:
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: mg/m^2 BID
800
5.Primary Outcome
Title Part 1: PRD of Erlotinib for Part 2
Hide Description Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
Time Frame Up to Week 6 (Cycle 1-3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population.
Arm/Group Title Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
Hide Arm/Group Description:
Dose-escalation was performed using a substance related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DL-1, 2, 3, 4, 5 and 6) were administered with either 100 mg or 150 mg of erlotinib daily orally, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: mg/day
150
6.Primary Outcome
Title Part 1: PRD of Bevacizumab for Part 2
Hide Description Once the MTD was reached then the preceding lower dose level was used as PRD. MTD for each of the medications was defined as the lowest dose studied which resulted in DLT in at least 33% of participants of the same quality category. DLT was defined as >= G3 or G4 toxicity; >= G3 non-hematological toxicities directly related to study treatment (other than untreated nausea/vomiting, alopecia, G3/G4 bilirubinemia for less than 7 days due to edema of the ductus choledochus and anemia); G4 thrombocytopenia, neutropenia lasting >= 7 days or G3 thrombocytopenia with complications, requiring transfusions, febrile neutropenia; stopping of oral CAP and/or ERL intake for >= 7 days, and/or cancellation of one or more BEV infusion(s) due to AEs. If MTD was not defined for a drug treatment then the maximum planned dose of that particular drug was considered as PRD for Part 2.
Time Frame Up to Week 6 (Cycle 1-3)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population.
Arm/Group Title Triple Combination (Bevacizumab/Erlotinib/Capecitabine)
Hide Arm/Group Description:
Dose-escalation was performed using a substance-related toxicity-based dose escalation scheme and was started with capecitabine followed by erlotinib and completed by bevacizumab. Participants in different dose levels (DLs - 1, 2, 3, 4, 5 and 6) were administered either 100 mg or 150 mg of erlotinib tablet orally daily, 5 mg/kg or 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and any of the different doses of capecitabine BID (500/650/800/900 mg/m^2) orally. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 30
Measure Type: Number
Unit of Measure: mg/kg Q2W
10
7.Secondary Outcome
Title Part 1: Maximum Serum Concentration (Cmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR] and 5'-Deoxy-5-Fluorouridine [5'-DFUR])
Hide Description [Not Specified]
Time Frame CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description:
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 6 6 6 3 3
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (µg/mL)
Erlotinib (n=6,6,6,6,3,3) 1.50  (1.21) 0.95  (0.58) 0.68  (0.34) 0.93  (0.63) 0.58  (0.15) 1.69  (0.67)
OSI-420 (n=6,6,6,6,3,3) 0.09  (0.07) 0.05  (0.03) 0.04  (0.02) 0.06  (0.04) 0.03  (0.01) 0.10  (0.02)
Capecitabine (n=6,6,6,6,3,3) 1.69  (1.22) 1.13  (0.61) 4.89  (4.23) 5.48  (4.51) 9.47  (5.19) 9.9  (5.01)
5'-DFCR (n=5,5,6,6,3,3) 3.5  (3.02) 4.28  (1.61) 11.46  (5.32) 6.26  (2.05) 5.44  (2.43) 4.15  (1.24)
5'-DFUR (n=4,5,6,6,3,3) 7.9  (4.41) 7.3  (2.74) 6.17  (2.63) 7.24  (3.35) 3.28  (0.72) 5.1  (2.35)
8.Secondary Outcome
Title Part 1: Time to Reach Cmax (Tmax) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Hide Description [Not Specified]
Time Frame CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description:
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 6 6 6 3 3
Median (Full Range)
Unit of Measure: hours (h)
Erlotinib (n=6,6,6,6,3,3)
2.50
(1.00 to 8.00)
2.00
(2.00 to 8.00)
2.00
(1.00 to 6.00)
3.00
(2.00 to 8.00)
5.00
(4.00 to 6.00)
2.00
(2.00 to 3.00)
OSI-420 (n=6,6,6,6,3,3)
3.00
(1.00 to 8.00)
2.00
(2.00 to 24.00)
2.00
(1.00 to 8.00)
7.00
(2.00 to 24.00)
6.00
(6.00 to 6.00)
4.00
(2.00 to 4.00)
Capecitabine (n=6,6,6,6,3,3)
0.5
(0.5 to 5)
1
(0.5 to 3)
1.5
(0.5 to 3)
0.75
(0.5 to 2)
1
(0.5 to 2)
0.5
(0.5 to 1)
5'-DFCR (n=5,5,6,6,3,3)
0.5
(0.5 to 2.5)
1
(1 to 1.5)
1.5
(0.5 to 2.5)
1
(0.5 to 2)
1
(0.5 to 2.5)
1.5
(0.5 to 2.5)
5'-DFUR (n=4,5,6,6,3,3)
1
(1 to 2.5)
1.5
(1 to 2)
1.5
(0.5 to 2.5)
1.5
(0.5 to 2)
1
(0.5 to 2.5)
1.5
(1 to 2)
9.Secondary Outcome
Title Part 1: Last Quantifiable Drug Concentration (Clast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Hide Description [Not Specified]
Time Frame CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description:
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 6 6 6 3 3
Mean (Standard Deviation)
Unit of Measure: µg/mL
Erlotinib (n=6,6,6,6,3,3) 0.37  (0.36) 0.31  (0.19) 0.23  (0.11) 0.39  (0.39) 0.23  (0.02) 0.52  (0.19)
OSI-420 (n=6,6,6,6,3,3) 0.04  (0.06) 0.02  (0.01) 0.01  (0.01) 0.04  (0.04) 0.01  (0.00) 0.04  (0.01)
Capecitabine (n=6,6,6,6,3,3) 0.05  (0.06) 0.2  (0.2) 0.17  (0.15) 0.06  (0.03) 0.29  (0.26) 0.17  (0.1)
5'-DFCR (n=5,5,6,6,3,3) 0.23  (0.23) 0.08  (0.04) 0.64  (0.6) 0.75  (0.89) 0.99  (1.22) 0.3  (0.1)
5'-DFUR (n=4,5,6,6,3,3) 2.54  (0.14) 1.03  (1.05) 0.77  (0.92) 0.58  (0.49) 0.14  (0.08) 0.14  (0.05)
10.Secondary Outcome
Title Part 1: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUClast) of Erlotinib and Its Metabolite OSI-420 (CP373420), Capecitabine and Its Metabolites (5'-DFCR and 5'-DFUR)
Hide Description [Not Specified]
Time Frame CAP: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6 hours (h) of every 2-week cycle (until Week 259) ERL: 2, 3 4, 5, 6, 7, 8, 10, 24, 28, 48, 52, 72, 76, 96, 100, 120, 124, 144, 148, 168 and 172 h of every 2-week cycle (until Week 259)
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Hide Analysis Population Description
Per-protocol population. Here "n" signifies the number of participants who were evaluable for each drug for each arm, respectively.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description:
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 6 6 6 6 3 3
Mean (Standard Deviation)
Unit of Measure: h*µg/mL
Erlotinib (n=6,6,6,6,3,3) 15.81  (12.91) 11.06  (5.41) 9.15  (4.39) 13.07  (11.03) 8.54  (1.96) 19.88  (4.75)
OSI-420 (n=6,6,6,6,3,3) 1.15  (1.21) 0.48  (0.35) 0.41  (0.18) 0.99  (0.73) 0.36  (0.03) 1.42  (0.17)
Capecitabine (n=6,6,6,6,3,3) 1.43  (1.02) 1.63  (1.01) 5.88  (6.28) 5.28  (3.25) 13.63  (8.63) 9.74  (3.02)
5'-DFCR (n=5,5,6,6,3,3) 3.97  (2.65) 7.01  (1.89) 20.27  (11.53) 9.35  (3.26) 12.63  (9.89) 8.06  (2.14)
5'-DFUR (n=4,5,6,6,3,3) 15.42  (9.45) 13.58  (7.84) 9.76  (4.60) 10.86  (4.96) 5.17  (0.89) 8.53  (1.87)
11.Secondary Outcome
Title Part 2: Percentage of Participants Free From Disease Progression
Hide Description As per Response Evaluation Criteria In Solid Tumors (RECIST) version (v) 1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions (target and non-target lesions) or the unequivocal progression of existing non-target lesions.
Time Frame Month 6
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Hide Analysis Population Description
Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description:
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Part 2: Percentage of Participants With Disease Control
Hide Description A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) during the assessment. As per RECIST v1.1, CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the screening sum longest diameter; SD for target lesions is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started and SD for non-target lesions defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
Time Frame From baseline thereafter, every 6 weeks (±7 days), then 1 week after last dose (follow-up), thereafter every 6 weeks (±7 days) until disease progression (up to Week 259)
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Hide Analysis Population Description
Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description:
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Part 2: Percentage of Participants With Clinical Benefit Response
Hide Description Clinical benefit response was defined as a composite of pain control, Karnofsky performance status (KPS), and weight. The KPS allows participants to be classified as per their functional impairment (abnormal function). It was recorded on an 11-point scale; 0= “dead” to 100= “Normal, no complaints, no evidence of disease” and sub-divided to 3 categories; 0 to 40 = “Unable to care for self, requires institutional or hospital care or equivalent, disease may be rapidly progressing”; 50 to 70= “Unable to work, able to live at home and care for most personal needs, varying amount of assistance needed and 80 to 100= “Able to carry on normal activity; no special care is needed”.
Time Frame One week before start of study treatment and weekly until disease progression or death (Up to Week 259)
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Hide Analysis Population Description
Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description:
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Part 2: Overall Survival
Hide Description Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive.
Time Frame From baseline until death (Up to Week 259)
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Hide Analysis Population Description
Data was not reported as there were no participants analyzed since Part 2 of the study was not fully implemented.
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description:
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID orally within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From screening up to 30 days after the last chemotherapy treatment.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Hide Arm/Group Description Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 500 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 650 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 100 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 900 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 5 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity. Participants were administered oral 150 mg of erlotinib tablet daily at least 1 hour before or 2 hours after the ingestion of food, 10 mg/kg of bevacizumab IV infusion on Day 1 of each cycle (1 Cycle = 2 Weeks), and oral 800 mg/m^2 of capecitabine tablet BID within 30 minutes after the ingestion of food. All the medications were continued until confirmed evidence of disease progression or unacceptable toxicity.
All-Cause Mortality
ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/6 (50.00%)   2/6 (33.33%)   4/6 (66.67%)   5/6 (83.33%)   3/3 (100.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders             
Anemia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Bilirubinaemia * 2  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Embolism pulmonary * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hyponatremia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Cardiac disorders             
Myocardial infarction * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Gastrointestinal disorders             
Abdominal pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Diarrhoea * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Dysphagia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Gastrointestinal haemorrhage * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Haemorrhage rectum * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Intestinal stenosis * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Nausea * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Vomiting * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
General disorders             
Fatigue * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Fever * 1  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Pain * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Syncope * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hepatobiliary disorders             
Hepatic function abnormal * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Infections and infestations             
Infection * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Sepsis * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Musculoskeletal and connective tissue disorders             
Skeletal pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Nervous system disorders             
Aphasia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Vertigo * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  1/3 (33.33%) 
Respiratory, thoracic and mediastinal disorders             
Dyspnoea * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Pneumonia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders             
Dermatitis * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Vascular disorders             
Thrombophlebitis * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.0)
2
Term from vocabulary, MedDRA (16.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ERL+BEV+CAP Dose Level-1 ERL+BEV+CAP Dose Level-2 ERL+BEV+CAP Dose Level-3 ERL+BEV+CAP Dose Level-4 ERL+BEV+CAP Dose Level-5 ERL+BEV+CAP Dose Level-6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   5/6 (83.33%)   6/6 (100.00%)   6/6 (100.00%)   3/3 (100.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders             
Anemia * 1  2/6 (33.33%)  0/6 (0.00%)  2/6 (33.33%)  3/6 (50.00%)  1/3 (33.33%)  1/3 (33.33%) 
Bilirubin * 1  1/6 (16.67%)  2/6 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Coagulation time decreased * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Epistaxis * 1  1/6 (16.67%)  1/6 (16.67%)  3/6 (50.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Gingival bleeding * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hypocalcaemia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hypokalaemia * 1  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hypoproteinemia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Thrombocytopenia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Thrombosis * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Endocrine disorders             
Hyperthyroidism * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Eye disorders             
Conjunctivitis * 1  0/6 (0.00%)  3/6 (50.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Gastrointestinal disorders             
Abdominal pain * 1  3/6 (50.00%)  4/6 (66.67%)  3/6 (50.00%)  2/6 (33.33%)  1/3 (33.33%)  0/3 (0.00%) 
Cheilitis * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Colitis * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Constipation * 1  2/6 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%) 
Diarrhoea * 1  2/6 (33.33%)  4/6 (66.67%)  4/6 (66.67%)  4/6 (66.67%)  0/3 (0.00%)  2/3 (66.67%) 
Dyspepsia * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Dysphagia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  1/3 (33.33%) 
Flatulence * 1  1/6 (16.67%)  2/6 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Gastrointestinal disorder nos * 1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hematemesis * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hiccup * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Melena * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Mouth dry * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Nausea * 1  4/6 (66.67%)  2/6 (33.33%)  4/6 (66.67%)  4/6 (66.67%)  2/3 (66.67%)  2/3 (66.67%) 
Esophagitis * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Stomatitis * 1  1/6 (16.67%)  1/6 (16.67%)  3/6 (50.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Toothache * 1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Vomiting * 1  1/6 (16.67%)  3/6 (50.00%)  4/6 (66.67%)  4/6 (66.67%)  1/3 (33.33%)  1/3 (33.33%) 
General disorders             
Back pain * 1  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Common cold * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Exsiccosis * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Fatigue * 1  6/6 (100.00%)  3/6 (50.00%)  3/6 (50.00%)  3/6 (50.00%)  2/3 (66.67%)  2/3 (66.67%) 
Fever * 1  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Leg pain * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Oedema * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Oedema mouth * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Oedema peripheral * 1  2/6 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Pain * 1  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Rigors * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  0/3 (0.00%) 
Syncope * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Temperature changed sensation * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Hepatobiliary disorders             
Ascites * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hepatic function abnormal * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Infections and infestations             
Herpes simplex * 1  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Infection * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Moniliasis * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Skin infection * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Wound dehiscence * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Investigations             
C- reactive protein positive * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Metabolism and nutrition disorders             
Appetite loss * 1  4/6 (66.67%)  1/6 (16.67%)  2/6 (33.33%)  4/6 (66.67%)  0/3 (0.00%)  1/3 (33.33%) 
Diabetes mellitus * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Hyperuricemia * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Weight decrease * 1  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  3/6 (50.00%)  0/3 (0.00%)  0/3 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Muscle weakness * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Skeletal pain * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%) 
Nervous system disorders             
Dysphonia * 1  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  2/6 (33.33%)  1/3 (33.33%)  1/3 (33.33%) 
Headache * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Neuropathy peripheral * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Taste perversion * 1  1/6 (16.67%)  1/6 (16.67%)  2/6 (33.33%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Vertigo * 1  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  2/3 (66.67%)  1/3 (33.33%) 
Psychiatric disorders             
Anxiety * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Depression * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Sleep disorder * 1  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Renal and urinary disorders             
Albuminuria * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Urinary tract infection * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  1/3 (33.33%) 
Reproductive system and breast disorders             
Genital ulceration * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Vaginitis * 1  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Bronchitis * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Coughing * 1  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Dyspnoea * 1  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  2/6 (33.33%)  0/3 (0.00%)  1/3 (33.33%) 
Increased pulmonary secretion * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Rhinitis * 1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/3 (0.00%)  2/3 (66.67%) 
Skin and subcutaneous tissue disorders             
Alopecia * 1  2/6 (33.33%)  2/6 (33.33%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Bullous eruption * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%) 
Dermatitis * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Mucosis left breast * 1  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Palmar-plantar erythrodyesthesia * 1  2/6 (33.33%)  5/6 (83.33%)  3/6 (50.00%)  3/6 (50.00%)  1/3 (33.33%)  0/3 (0.00%) 
Paronychia * 1  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  0/3 (0.00%) 
Pruritus * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Rash * 1  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Rash erythematous * 1  3/6 (50.00%)  5/6 (83.33%)  4/6 (66.67%)  4/6 (66.67%)  2/3 (66.67%)  2/3 (66.67%) 
Skin discolouration * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Skin dry * 1  0/6 (0.00%)  3/6 (50.00%)  0/6 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  0/3 (0.00%) 
Skin reaction localized * 1  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Sweating increased * 1  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Vascular disorders             
Hypertension * 1  1/6 (16.67%)  1/6 (16.67%)  1/6 (16.67%)  2/6 (33.33%)  0/3 (0.00%)  1/3 (33.33%) 
Hypertension aggravated * 1  2/6 (33.33%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Thrombophlebitis * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
 * 1  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Planned Part 2 of the study was not implemented and outcome measures related to Part 2 were not analyzed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00925769     History of Changes
Other Study ID Numbers: ML20784
2008-004444-36
First Submitted: April 15, 2009
First Posted: June 22, 2009
Results First Submitted: July 13, 2015
Results First Posted: August 7, 2015
Last Update Posted: August 7, 2015