Evaluation of Bevacizumab Combined With First Line Chemotherapy in Patients Aged 75 and Over Suffering From Metastatic Colorectal Adenocarcinoma. Phase II Randomized - Intergroup Trial: FFCD, FNCLCC, GERICO
Overview
- Phase
- Phase 2
- Intervention
- Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen) + bevacizumab
- Conditions
- Colorectal Cancer
- Sponsor
- Federation Francophone de Cancerologie Digestive
- Enrollment
- 102
- Locations
- 1
- Primary Endpoint
- Tolerance, in terms of no grade 4 arterial hypertension, grade 3-4 thromboembolic event, grade 3-4 cardiac insufficiency, and hospitalization not related to chemotherapy
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving bevacizumab together with combination chemotherapy may be a better way to block tumor growth. It is not yet known whether combination chemotherapy is more effective when given together with or without bevacizumab in treating patients with colorectal cancer.
PURPOSE: This randomized phase II trial is studying the side effects of giving bevacizumab together with first-line chemotherapy and to see how well it works in treating older patients with metastatic colorectal cancer.
Detailed Description
OBJECTIVES: Primary * To evaluate composite efficacy and safety, in terms of objective response or tumoral stability by RECIST criteria and no deterioration in the Spitzer QoL Index score of ≥ 2 points at 4 months, in older patients with unresectable metastatic colorectal adenocarcinoma treated with bevacizumab and first-line chemotherapy. * To evaluate tolerance, in terms of no grade 4 arterial hypertension, grade 3-4 thromboembolic event, grade 3-4 cardiac insufficiency, and hospitalization not linked to chemotherapy, in these patients. Secondary * To evaluate toxicity in these patients. * To assess time to deterioration of autonomy in these patients. * To assess survival with no deterioration of autonomy of these patients. * To evaluate time to deterioration of quality of life of these patients. * To evaluate percentage of patients who received at least 2/3 of the protocol treatment at month 4. * To assess time to treatment failure in these patients. * To assess progression-free survival and global survival of these patients. Tertiary * To test for predictive factors of treatment success identified during the geriatric evaluation, according to the main judgment criterion, and analysis of the evolution of geriatric parameters during follow-up int these patients. (Exploratory) OUTLINE: This is a multicenter study. Patients are stratified according to chemotherapy (monotherapy vs double chemotherapy), primary tumor (resected vs non-resected), and quality-of-life score evaluated by the Spitzer QoL Index (0-3 vs 4-7 vs 8-10). Patients are randomized to 1 of 2 treatment arms. * Arm A: Patients receive 1 of the following regimens according to the discretion of the investigator: * Simplified LV5FU2 comprising leucovorin calcium IV over 2 hours on days 1 and 15 and fluorouracil IV over 46 hours beginning on days 1 and 15. * FOLFIRI comprising leucovorin calcium IV over 2 hours on days 1 and 15; irinotecan hydrochloride IV over 2 hours on days 1 and 15; and fluorouracil IV over 46 hours beginning on days 1 and 15. * FOLFOX4 comprising oxaliplatin IV over 2 hours on days 1 and 15; leucovorin calcium IV over 2 hours on days 1 and 15; and fluorouracil IV over 46 hours beginning on days 1 and 15. All treatment regimens repeat every 4 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity. * Arm B: Patients receive chemotherapy as in arm A. Patients also receive bevacizumab IV over 90 minutes on days 1 and 15. Treatment repeats every 4 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity. Quality of life is assessed periodically. Blood specimens are collected for evaluation of the quantification of circulating cells for early prediction of response to treatment. After completion of study therapy, patients are followed up every 2-3 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Chemotherapy associated with bevacizumab
Chemotherapy (FOLFIRI, FOLFOX, LV5FU2) associated with bevacizumab
Intervention: Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen) + bevacizumab
Chemotherapy
Chemotherapy (FOLFIRI, FOLFOX, LV5FU2)
Intervention: Chemotherapy ( FOLFIRI regimen, FOLFOX regimen or LV5FU2 regimen)
Outcomes
Primary Outcomes
Tolerance, in terms of no grade 4 arterial hypertension, grade 3-4 thromboembolic event, grade 3-4 cardiac insufficiency, and hospitalization not related to chemotherapy
Time Frame: 4 months
Deterioration in the Spitzer QoL Index score of ≥ 2 points at baseline and at 4 months
Time Frame: 4 months
Efficacy, in terms of objective response or tumoral stability by RECIST criteria
Time Frame: 4 months
Secondary Outcomes
- Survival with no deterioration of autonomy(4 months)
- Toxicity(4 months)
- Time to deterioration of autonomy(4 months)