A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Pfizer
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01925274
First received: August 15, 2013
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

This study will investigate whether the combination of PF-05212384 plus Irinotecan improves progression free survival in patients with KRAS and NRAS wild type metastatic colorectal cancer when compared with the combination of cetuximab plus Irinotecan. A Japanese Lead in Cohort will assess the safety of the combination of PF-05212384 + irinotecan in patients enrolled at Japanese sites.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: PF-05212384
Drug: irinotecan
Drug: Cetuximab
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Study Of PF-05212384 Plus Irinotecan Versus Cetuximab Plus Irinotecan In Patients With KRAS and NRAS Wild Type Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: 36 weeks ] [ Designated as safety issue: No ]
    Median time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (Weeks) = (first event date minus first dose date plus 1) divided by 7


Secondary Outcome Measures:
  • Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Determination of unacceptable toxicity in patients enrolled at sites in Japan.

  • Number of Participants With Objective Response [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

  • Duration of Response (DR) [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

  • Overall Survival (OS) [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Overall survival was the duration from enrollment to death. For participants who are alive, overall survival was censored at the last contact.

  • Number of Participants Using Healthcare Resources [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    FACT-C

  • Area under the Concentration-Time Curve (AUC) [ Time Frame: 0, 1, 2, 4, 6, 24, 72, 120 hours ] [ Designated as safety issue: No ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0, 1, 2, 4, 6, 24, 72, 120 hours ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0, 1, 2, 4, 6, 24, 72, 120 hours ] [ Designated as safety issue: No ]
  • Levels of signaling proteins in paired and single tumor biopsies [ Time Frame: 0, 36, 37 ] [ Designated as safety issue: No ]
  • Gene sequences and/or gene copy numbers in paired tumor biopsies [ Time Frame: 0, 36, 37 ] [ Designated as safety issue: No ]

Estimated Enrollment: 159
Study Start Date: November 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
PF-05212384 plus Irinotecan
Drug: PF-05212384
30 minute IV infusion of PF-05212384 on days 2, 9, 16 and 23 of each cycle. Intra-patient dose escalation will commence with 110mg and will increase depending on tolerability.
Other Name: PKI-587
Drug: irinotecan
90 minutes IV infusion of irinotecan 180mg/m^2 on days 1 and 15 of each cycle
Other Name: Camptosar, Campto, CPT-11
Active Comparator: Arm B
Cetuximab plus Irinotecan
Drug: Cetuximab
120 minute IV infusion of cetuximab 400mg/m^2 on cycle 1 day 1; 60 minute IV infusion of cetuximab on days 8, 15, and 22 of each cycle, and on day 1 of each cycle after cycle 1
Other Name: Erbitux
Drug: Irinotecan
90 minutes IV infusion of Irinotecan 180mg/m^2 on days 1 and 15 of each cycle
Other Name: Camptosar, Campto, CPT-11

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • KRAS and NRAS wild type metastatic colorectal cancer
  • Progression following treatment for colorectal cancer with irinotecan, oxaliplatin and fluoropyrimidine therapy in the metastatic setting.
  • Eastern Cooperative Oncology Group [ECOG] Performance Status of 0, 1, or 2
  • At least one measurable lesion by Response Evaluation Criterion in Solid Tumors [RECIST]

Exclusion Criteria:

  • More than 2 prior cytotoxic chemotherapy regimens for metastatic colorectal cancer.
  • Prior treatment with a PI3K, mTOR, AKT or EGFR inhibitor
  • Patients who have discontinued treatment with prior irinotecan therapy due to toxicity.
  • Prior radiation to the pelvis or abdomen
  • Patients with history of interstitial lung disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01925274

Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021

  Show 64 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01925274     History of Changes
Other Study ID Numbers: B2151005
Study First Received: August 15, 2013
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
metastatic colorectal cancer
colorectal cancer
KRAS
colon cancer
mCRC
CRC
PF-05212384
KRAS wild type colorectal cancer
irinotecan
cetuximab
NRAS

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Camptothecin
Cetuximab
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 21, 2014