Phase II Study Evaluating the Efficacy and Tolerance to Chemotherapy With 5-fluorouracil, Folinic Acid, Irinotecan and Bevacizumab as First-line Treatment in Patients With Metastatic Colorectal Cancer
Phase II Study Evaluating the Efficacy and Tolerance to Chemotherapy With 5-fluorouracil, Folinic Acid, Irinotecan and Bevacizumab as First-line Treatment in Patients With Metastatic Colorectal Cancer
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, such as irinotecan, leucovorin, and fluorouracil, 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.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with combination chemotherapy works as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a nonrandomized, multicenter study.
Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Blood and tissue samples are collected periodically for pharmacogenetic and genetic polymorphism analysis.
PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the colon or rectum
Metastatic, unresectable disease
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:
No infection or serious noncancerous disease
No condition that is unstable or would increase risk to the patient, including any of the following:
No familial, geographical, social, or psychological condition that would preclude study participation
No prisoners or patients without guardians
PRIOR CONCURRENT THERAPY: