FOLFIRI or FOLFOX With or Without Cetuximab in Patients With Metastatic Adenocarcinoma of the Colon or Rectum
- Conditions
- Colorectal Cancer
- Interventions
- Registration Number
- NCT00077233
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This is a randomized phase II study trial that has served as a screening trial to test the increased efficacy of chemotherapy + cetuximab versus chemotherapy alone among patients with untreated, advanced or metastatic colon cancer regardless of tumor status with respect to EGFR.
- Detailed Description
CALGB 80203 was activated on December 15, 2003. In February 2004, based on the results of the randomized trial of IFL +/- cetuximab showing a significant improvement in overall survival with cetuximab, cetuximab was approved by the FDA for use as front-line therapy for patients with metastatic colon cancer. In response to this action, the Data Safety and Monitoring Board recommended closure of CALGB 80203. CALGB 80203 was subsequently closed to accrual in January 2005 with 238 of the originally targeted 2200 patients enrolled. A final decision was to "replace" CALGB 80203 with a three-treatment arm randomized trial of chemotherapy (FOLFOX or FOLFIRI) with and without cetuximab and/or bevacizumab. The protocol was amended to allow analysis of the data from CALGB 80203 as a randomized phase II trial and reporting of the results.
Patients were stratified according to prior adjuvant chemotherapy (yes vs no) and prior pelvic radiation (yes vs no). Patients must have completed any major surgery or radiotherapy (eg, chest or bone palliative RT or pelvic RT) ≥ 4 weeks from registration and completed any minor surgery ≥ 2 weeks from registration. Patients must have fully recovered from the procedure and/or radiotherapy. Patients must have initiated treatment within 7 days of registration. Patients were randomized to 1 of 4 treatment arms, please see a description of the treatment regimens in the "Arms" section. In addition, patients received concomitant and supportive therapy as appropriate per the protocol.
OBJECTIVES:
Primary
1. To determine if the addition of C225 to FOLFIRI or FOLFOX chemotherapy prolongs survival of patients with untreated, advanced or metastatic colorectal cancer.
Secondary
1. To determine if the FOLFIRI and FOLFOX regimens are equivalent in terms of survival as front-line therapy for advanced colorectal patients.
2. To determine the level of EGFR expression in patients with metastatic colorectal cancer.
Patients were followed up to 3 years post-treatment.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 238
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: FOLFIRI irinotecan Patients receive irinotecan 180 mg/m\^2 over 90 minutes on day 1, then leucovorin 400 mg/m\^2 over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. One cycle of therapy is 8 weeks. Arm A: FOLFIRI 5-FU Patients receive irinotecan 180 mg/m\^2 over 90 minutes on day 1, then leucovorin 400 mg/m\^2 over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. One cycle of therapy is 8 weeks. Arm A: FOLFIRI leucovorin Patients receive irinotecan 180 mg/m\^2 over 90 minutes on day 1, then leucovorin 400 mg/m\^2 over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. One cycle of therapy is 8 weeks. Arm B: FOLFIRI + C225 cetuximab Patients receive irinotecan 180 mg/m\^2 over 90 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Arm B: FOLFIRI + C225 5-FU Patients receive irinotecan 180 mg/m\^2 over 90 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Arm B: FOLFIRI + C225 irinotecan Patients receive irinotecan 180 mg/m\^2 over 90 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Arm C: FOLFOX leucovorin Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks. Arm B: FOLFIRI + C225 leucovorin Patients receive irinotecan 180 mg/m\^2 over 90 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5FU 400 mg/m\^2 IV bolus injection then 5FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours repeated every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Arm C: FOLFOX 5-FU Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks. Arm C: FOLFOX oxaliplatin Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 IV over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks. Arm D: FOLFOX + C225 cetuximab Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Arm D: FOLFOX + C225 5-FU Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Arm D: FOLFOX + C225 leucovorin Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced. Arm D: FOLFOX + C225 oxaliplatin Patients receive oxaliplatin 85 mg/m\^2 IV infused over 120 minutes, then leucovorin 400 mg/m\^2 over 2 hours followed by 5 FU 400 mg/m\^2 IV bolus injection then 5 FU 2400 mg/m\^2 continuous IV infusion over 46-48 hours every 2 weeks. Patients also receive cetuximab 400 mg/m\^2 IV over 120 minutes day 1, then 250 mg/m\^2 IV over 60 minutes weekly. All patients must be premedicated with diphenhydramine hydrochloride 50 mg (or a similar agent) IV prior to the first dose of cetuximab in an effort to prevent a hypersensitivity reaction. Premedication is recommended prior to subsequent doses, but at the Investigator's discretion the dose of diphenhydramine (or a similar agent) may be reduced.
- Primary Outcome Measures
Name Time Method Overall survival Up to 3 years of follow up
- Secondary Outcome Measures
Name Time Method Progression-free survival Up to 18 months of follow up Partial response Up to 18 months of follow up Complete response Up to 18 months of follow up Proportion of patients experiencing ≥ Grade 3 ANC Up to 30 days post-treatment Percent of total dose administered Up to 30 days post-treatment Proportion of patients experiencing ≥ Grade 3 diarrhea Up to 30 days post-treatment Proportion of patients experiencing ≥ Grade 4 toxicity on each cetuximab treatment arm Up to 30 days post-treatment
Trial Locations
- Locations (77)
Northeast Alabama Regional Medical Center
🇺🇸Anniston, Alabama, United States
Rebecca and John Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Naval Medical Center - San Diego
🇺🇸San Diego, California, United States
Veterans Affairs Medical Center - San Diego
🇺🇸San Diego, California, United States
UCSF Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Veterans Affairs Medical Center - San Francisco
🇺🇸San Francisco, California, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Lombardi Cancer Center at Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Walter Reed Army Medical Center
🇺🇸Washington, District of Columbia, United States
Scroll for more (67 remaining)Northeast Alabama Regional Medical Center🇺🇸Anniston, Alabama, United States