Overview

This trial is active, not recruiting.

Conditions colon cancer, colorectal cancer, rectal cancer, metastatic colorectal cancer
Treatments panitumumab, bevacizumab, mfolfox6
Phase phase 2
Targets EGFR, VEGF
Sponsor Amgen
Start date April 2009
End date May 2012
Trial size 285 participants
Trial identifier NCT00819780, 20070509

Summary

The primary objective of this study is to estimate the treatment effect on progression-free survival (PFS) of panitumumab relative to bevacizumab in combination with mFOLFOX6 chemotherapy as first-line therapy in patients with tumors expressing wild-type KRAS, unresectable mCRC.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants received 6 mg/kg panitumumab administered by intravenous (IV) infusion and modified FOLFOX6 (mFOLFOX6) chemotherapy regimen consisting of oxaliplatin (85 mg/m^2), leucovorin (400 mg/m^2) and 5-fluorouracil (5-FU) (2400 mg/m^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.
panitumumab Vectibix
Panitumumab is a fully human immunoglobulin G (IgG)2 monoclonal antibody antagonist directed against human Epidermal Growth Factor receptor (EGFr).
mfolfox6
mFOLFOX6 regimen is a combination therapy of oxaliplatin (85 mg/m^2) administered as a 2-hour infusion on Day 1; leucovorin (400 mg/m^2) administered as a 2-hour infusion on Day 1; followed by a loading dose of 5-fluorouracil (5-FU; 400 mg/m^2) IV bolus administered over approximately 2 to 4 minutes on Day 1, then 5- FU (2400 mg/m^2) via ambulatory pump administered for a period of 46 to 48 hours.
(Active Comparator)
Participants received 5 mg/kg bevacizumab administered by IV infusion and the mFOLFOX6 regimen consisting of oxaliplatin (85 mg/m^2), leucovorin (400 mg/m^2), followed by 5-FU (2400 mg/m^2) administered on Day 1 of every 14-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or death.
bevacizumab Avastin
Bevacizumab is a humanized monoclonal IgG1 antibody that is directed against Vascular Endothelial Growth Factor (VEGF).
mfolfox6
mFOLFOX6 regimen is a combination therapy of oxaliplatin (85 mg/m^2) administered as a 2-hour infusion on Day 1; leucovorin (400 mg/m^2) administered as a 2-hour infusion on Day 1; followed by a loading dose of 5-fluorouracil (5-FU; 400 mg/m^2) IV bolus administered over approximately 2 to 4 minutes on Day 1, then 5- FU (2400 mg/m^2) via ambulatory pump administered for a period of 46 to 48 hours.

Primary Outcomes

Measure
Progression-free Survival (PFS)
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.

Secondary Outcomes

Measure
Overall Survival
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Percentage of Participants With an Objective Response
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Duration of Response
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Time to Disease Progression
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Time to Initial Objective Response
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Resection Rate
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Progression-free Survival (PFS) in Participants With Wild-type Rat Sarcoma Viral Oncogene Homolog (RAS)
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Progression-free Survival (PFS) in Participants With Wild-type RAS / V-raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF)
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Overall Survival in Participants With Wild-type RAS
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Overall Survival in Participants With Wild-type RAS / BRAF
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Percentage of Participants With an Objective Response for Participants With Wild-type RAS
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Percentage of Participants With an Objective Response for Participants With Wild-type RAS / BRAF
time frame: From randomization until the data cutoff date of 30 May 2012; median follow-up time was 60 weeks.
Number of Participants With Adverse Events (AEs)
time frame: The time frame for adverse event reporting is from the first dose date to 30 days since the last dose date. The median time frame is 8.0 months for Panitumumab Plus mFOLFOX arm and 7.3 months for Bevacizumab Plus mFOLFOX6 arm.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histologically or cytologically-confirmed adenocarcinoma of the colon or rectum in patients with unresectable metastatic (M1) disease - Patients with at least 1 uni-dimensionally measurable lesion of at least 10 mm per modified Response Evaluation Criteria in Solid Tumors (RECIST) guidelines - Wild-type KRAS tumor status confirmed by an Amgen approved central laboratory or an experienced laboratory (local laboratory) per local regulatory guidelines using a validated test method - Eastern Cooperative Oncology Group (ECOG) score of 0 or 1 - Men or women 18 years of age or older - Adequate hematologic, renal, hepatic, metabolic, and coagulation function Exclusion Criteria: - History of prior or concurrent central nervous system (CNS) metastases - Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma - Clinically significant cardiac disease - Clinically significant peripheral sensory neuropathy - Active inflammatory bowel disease - Recent gastroduodenal ulcer to be active or uncontrolled - History of interstitial lung disease - Recent pulmonary embolism, deep vein thrombosis, or other significant venous event - Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy - Recent major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery.

Additional Information

Official title A Randomized, Multicenter, Phase 2 Study to Compare the Efficacy of Panitumumab in Combination With mFOLFOX6 to the Efficacy of Bevacizumab in Combination With mFOLFOX6 in Patients With Previously Untreated, KRAS Wild-Type, Unresectable, Metastatic Colorectal Cancer
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by Amgen.