Multicenter Phase III Randomized Study of FOLFIRI Plus Bevacizumab Following or Not by a Maintenance Therapy With Bevacizumab in Patients With Non-Pretreated Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- bevacizumab
- Conditions
- Colorectal Cancer
- Sponsor
- Federation Francophone de Cancerologie Digestive
- Enrollment
- 492
- Locations
- 58
- Primary Endpoint
- Disease-control duration
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of colorectal cancer by blocking blood flow to the tumor. It is not yet known whether giving more than one drug (combination chemotherapy) is more effective when given with or without bevacizumab in treating patients with metastatic colorectal cancer.
PURPOSE: This randomized phase III trial is studying giving combination chemotherapy with or without bevacizumab to see how well it works in treating patients with metastatic colorectal cancer.
Detailed Description
OBJECTIVES: Primary * Compare disease-control duration in patients with metastatic colorectal cancer receiving FOLFIRI chemotherapy in combination with bevacizumab with or without bevacizumab maintenance therapy. Secondary * Determine objective response rate. * Determine non-hematologic grade 3-4 (except alopecia) toxicity rate. * Determine overall toxicity rate. * Determine duration of chemotherapy-free interval. * Determine progression-free survival. * Determine overall survival. * Determine time-to-treatment failure. * Determine quality of life (EORTC QLQ-C30). * Complete geriatric evaluation. OUTLINE: This is a multicenter study. Patients are stratified according to cancer center, primary tumor (resected vs unresected), and Köhne criteria (low vs intermediate vs high). Patients are randomized to 1 of 2 treatment arms. * Arm A: Patients receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1-2. Chemotherapy treatment repeats every 2 weeks for 12 courses. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks during chemotherapy. Patients then receive bevacizumab maintenance therapy once every 2 weeks during the chemotherapy-free interval. * Arm B: Patients receive FOLFIRI chemotherapy and bevacizumab as in arm A. Patients receive no treatment during the chemotherapy-free interval. In all arms, the chemotherapy treatment and the chemotherapy-free interval treatment repeats in the absence of disease progression during the chemotherapy portion or unacceptable toxicity. Patients who progress during the chemotherapy-free interval will receive 12 more courses of chemotherapy. All patients complete quality of life questionnaires (QLQ-30) and patients ≥ 75 also complete the geriatric questionnaire at baseline and every 8 weeks during study treatment. After completion of study treatment, patients are followed up every 8 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
Intervention: bevacizumab
Maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
Intervention: FOLFIRI regimen
Maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
Intervention: fluorouracil
Maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
Intervention: irinotecan hydrochloride
Maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval maintenance with bevacizumab
Intervention: leucovorin calcium
No maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance
Intervention: bevacizumab
No maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance
Intervention: FOLFIRI regimen
No maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance
Intervention: fluorouracil
No maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance
Intervention: irinotecan hydrochloride
No maintenance with bevacizumab
FOLFIRI + Avastin and during the chemotherapy-free interval NO maintenance
Intervention: leucovorin calcium
Outcomes
Primary Outcomes
Disease-control duration
Time Frame: one year after last patient included
Secondary Outcomes
- Progression-free survival(one year after last patient is included)
- Rate of non-hematologic grade 3-4 toxicities (except alopecia)(one year after last patient is included)
- Overall toxicity rate(one year after last patient is included)
- Time-to-treatment failure(one year after last patient is included)
- Overall survival(one and 2 year after last patient is included)
- Geriatric evaluation(one year after last patient is included)
- Objective response rate(one year after last patient is included)
- Duration of chemotherapy-free interval(one year after last patient is included)
- Quality of life as assessed by EORTC QLQ-C30(one year after last patient is included)