Clinical trial NCT01925274: A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: metastatic colorectal cancer
colorectal cancer
KRAS
colon cancer
mCRC
CRC
PF-05212384
KRAS wild type colorectal cancer
irinotecan
cetuximab
NRAS
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-08-19
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Progression Free Survival (PFS) as Assessed by Investigators
timeFrame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Secondary outcomes:
measure: Number of Participants With Unacceptable Toxicity in Cycle 1 (Japanese LIC Only)
timeFrame: 28 days
measure: Percentage of Participants With Objective Response
timeFrame: 2 years
measure: Duration of Response
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Administration of the first dose of study drug through 28 calendar days after the last administration of study drug
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
timeFrame: Administration of the first dose of study drug through 28 calendar days after the last administration of study drug
measure: Number of Participants With Laboratory Test (Hematology) Abnormalities
timeFrame: 2 years
measure: Number of Participants With Laboratory Test (Chemistry) Abnormalities
timeFrame: 2 years
measure: Number of Participants With Laboratory Test (Urinalysis) Abnormalities
timeFrame: 2 years
measure: Number of Participants With Laboratory Test (Coagulation) Abnormalities
timeFrame: 2 years
measure: Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
timeFrame: 2 years
measure: Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
timeFrame: 2 years
measure: Maximum Plasma Concentration (Cmax) of PF-05212384
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
measure: Maximum Plasma Concentration (Cmax) of Irinotecan
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Maximum Plasma Concentration (Cmax) of SN-38
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Time for Maximum Plasma Concentration (Tmax) of PF-05212384
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
measure: Time for Maximum Plasma Concentration (Tmax) of Irinotecan
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Time for Maximum Plasma Concentration (Tmax) of SN-38
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Terminal Elimination Half Life (t½) of PF-05212384
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.
measure: Terminal Elimination Half Life (t½) of Irinotecan
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Terminal Elimination Half Life (t½) of SN-38
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of PF-05212384
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9.
measure: Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of Irinotecan
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of SN-38
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05212384
timeFrame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9.
measure: Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Irinotecan
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of SN-38
timeFrame: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.
measure: Levels of Signaling Proteins in Paired and Single Tumor Biopsies
timeFrame: 2 years
measure: Number of Participants With Expression of Pre-defined Gene Sequences in Biopsied Tumor Tissues
timeFrame: 2 years
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C)
timeFrame: 2 years
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
state: California
city: Los Angeles
country: United States
facility: Drug Management Only: UCLA West Medical Pharmacy, Att: Steven L Wong, Pharm D
state: California
city: Los Angeles
country: United States
facility: Drug Management Only: UCLA West Medical Pharmacy
state: California
city: Los Angeles
country: United States
facility: UCLA West Medical Pharmacy
state: California
city: Los Angeles
country: United States
facility: Regulatory Management Only: TRIO-US Central Administration
state: California
city: Los Angeles
country: United States
facility: TRIO-US Central Administration (Regulatory Management only)
state: California
city: Los Angeles
country: United States
facility: TRIO_US
state: California
city: Northridge
country: United States
facility: West Valley Hematology/Oncology Med Group
state: California
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St Peters
state: Missouri
city: Henderson
country: United States
facility: Regulatory Office: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Richland
country: United States
facility: Kadlec Medical Center
state: Washington
city: Richland
country: United States
facility: Outpatient Imaging Center
state: Washington
city: Spokane Valley
country: United States
facility: Spokane Valley Cancer Center
state: Washington
city: Spokane
country: United States
facility: Medical Oncology Associates, PS
state: Washington
city: Nagoya
country: Japan
facility: Aichi cancer center central hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital / Department of Internal Medicine
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: