Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery
RATIONALE: 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. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with bevacizumab in treating patients with colorectal cancer.
PURPOSE: This randomized phase II trial is studying bevacizumab to compare how well it works when given together with two different combination chemotherapy regimens as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Procedure: quality-of-life assessment
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Randomized Study of First-Line Therapy Comprising Bevacizumab and Irinotecan Hydrochloride, Leucovorin Calcium, and Fluorouracil (FOLFIRI) Versus Bevacizumab and Irinotecan Hydrochloride and Capecitabine (XELIRI) in Patients With Unresectable Metastatic Colorectal Cancer [ACCORD]|
- Progression-free survival at 6 months
- Percentage of objective responses
- Percentage of stable disease responses
- Duration of objective response and stable disease
- Progression-free survival
- Overall survival
- Quality of life
|Study Start Date:||January 2006|
- Compare the progression-free survival at 6 months in patients with unresectable metastatic colorectal cancer treated with first-line therapy comprising bevacizumab and irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) vs bevacizumab and irinotecan hydrochloride and capecitabine (XELIRI).
- Compare the toxicities of these regimens in these patients.
- Compare the objective response rate and duration of response in patients treated with these regimens.
- Compare the tumor control in patients treated with these regimens.
- Compare the progression-free and overall survival of patients treated with these regimens.
- Compare the quality of life of patients treated with these regimens.
OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center, WHO performance status (0 or 1 vs 2), age (< 65 years vs ≥ 65 years), and number of metastatic sites (1 vs ≥ 2). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive bevacizumab alone every 2 weeks in the absence of disease progression.
- Arm II: Patients receive bevacizumab IV over 30-90 minutes and irinotecan hydrochloride IV over 90 minutes on day 1 and oral capecitabine on days 1-14. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may then continue to receive bevacizumab alone every 3 weeks in the absence of disease progression.
Quality of life is assessed periodically.
After completion of study therapy, patients are followed periodically.
PROJECTED ACCRUAL: A total of 144 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00423696
|C.H.U. de Brest|
|Brest, France, 29200|
|Centre Regional Francois Baclesse|
|Caen, France, 14076|
|Centre de Lutte Contre le Cancer Georges-Francois Leclerc|
|Dijon, France, 21079|
|Centre Oscar Lambret|
|Lille, France, 59020|
|Polyclinique des Quatre Pavillons|
|Lormont, France, 33310|
|Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes|
|Marseille, France, 13273|
|Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle|
|Montpellier, France, 34298|
|Centre Antoine Lacassagne|
|Nice, France, 06189|
|Institut Curie Hopital|
|Paris, France, 75248|
|Perigueux, France, 24004|
|Institut Jean Godinot|
|Reims, France, 51056|
|Centre Eugene Marquis|
|Rennes, France, 35062|
|Centre Rene Huguenin|
|Saint Cloud, France, 92210|
|Centre Alexis Vautrin|
|Vandoeuvre-les-Nancy, France, 54511|
|Institut Gustave Roussy|
|Villejuif, France, F-94805|
|Study Chair:||Michel Ducreux, MD, PhD||Gustave Roussy, Cancer Campus, Grand Paris|