Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery (OMEGA)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, recurrent colon cancer, recurrent rectal cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the colon or rectum
- No other histological types
Metastatic, unresectable disease
- No bone metastases only
- Unidimensionally measurable metastatic disease
- No CNS metastases
PATIENT CHARACTERISTICS:
- WHO performance status (PS) 0-2 OR Karnofsky PS 70-100%
- Life expectancy ≥ 12 weeks
- ANC > 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 10 g/dL
- Bilirubin ≤ 1.25 times normal (1.5 times normal in presence of hepatic metastases)
- AST and ALT < 3 times normal (5 times normal in presence of hepatic metastases)
- Creatinine < 1.25 times normal
- No proteinuria
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other cancer in the past 5 years except for carcinoma in situ of the uterine cervix or basal cell skin cancer
- No hypersensitivity to fluorouracil
- No hypersensitivity to leucovorin calcium, bevacizumab, or their excipients
- No hypersensitivity to Chinese hamster ovarian cell products or other recombinant humanized or nonhumanized monoclonal antibodies
- No allergy to irinotecan hydrochloride
- No prior reaction to attenuated vaccines (fever, jaundice)
- No poor nutritional status
- No Biermer anemia or other anemia due to vitamin B12 deficiency
- No uncontrolled symptomatic occlusion or subocclusion
- No medullary hypoplasia or severe insufficiency
- No prior chronic intestinal disease
- No Gilbert's syndrome
- No intra-abdominal inflammatory reaction (e.g., gastroduodenal ulcer, diverticulitis, or colitis)
- No chronic intestinal inflammatory disease
No thromboembolic arterial condition in the past 6 months, including any of the following:
- Cardiovascular accident
- Transient ischemic attack
- Myocardial infarction
- No infection or serious noncancerous disease
No condition that is unstable or would increase risk to the patient, including any of the following:
- Unstable angina
- Poorly controlled hypertension
- Severe cardiac insufficiency
- Serious arrhythmia
- Bleeding diathesis
- Pulmonary disease at risk of decompensation
- No familial, geographical, social, or psychological condition that would preclude study participation
- No prisoners or patients without guardians
PRIOR CONCURRENT THERAPY:
- At least 8 weeks since prior surgery
- At least 6 months since prior adjuvant chemotherapy
- At least 1 month since prior palliative chemotherapy
- No prior abdominal or pelvic radiotherapy
- At least 30 days since prior participation in another investigational study
- No prior bevacizumab
- No extensive intestinal resection (e.g., partial colectomy or extensive thin resection)
- No concurrent warfarin, Hypericum perforatum (St. John's wort), or prophylactic phenytoin
Sites / Locations
- Institut Bergonie
Arms of the Study
Arm 1
Experimental
Folfiri and Bevacizumab
Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. FOLFIRI (simplified LV5FU2 + irinotecan): Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated.