Bevacizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal cancer

  • Metastatic disease that is not amenable to surgery
• At least one measurable lesion according to RECIST criteria
• No untreated brain metastases or spinal cord compression

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Hemoglobin ≥ 9.0 g/dL
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
• Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
• PT-INR/PTT < 1.5 times ULN
• Creatinine clearance > 50 mL/min OR serum creatinine ≤ 1.5 times ULN
• Proteinuria on dipstick urinalysis < 2+ OR 24-hour urine protein ≤ 1g
• Not pregnant or nursing
• Negative pregnancy test
• Must be accessible for treatment and follow-up
• No history of inflammatory bowel disease and/or acute or subacute bowel occlusion
• No serious non-healing wound, ulcer, or bone fracture
• No evidence of bleeding diathesis or coagulopathy
• No uncontrolled hypertension

• No clinically significant cardiovascular disease including any of the following:

  • Cerebrovascular accident within the past 6 months
  • Myocardial infarction within the past 6 months
  • Unstable angina
  • New York Heart Association grade II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
• No known allergy to Chinese hamster ovary cell proteins or any of the components of the study medications
• No other malignancy within the past 5 years except basal cell and squamous cell skin cancer or carcinoma in situ of the cervix
• No significant traumatic injury within the past 28 days
• No substance abuse or medical, psychological, or social conditions that may interfere with participation in the study or the evaluation of study results
• Able to swallow oral medications

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 6 months since prior adjuvant treatment
• No prior irinotecan and/or bevacizumab during prior adjuvant therapy
• No prior cytotoxic drugs for the metastatic disease
• More than 10 days since prior and no concurrent anticoagulants for therapeutic purposes
• No chronic, daily treatment with high-dose aspirin (> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration
• No treatment with any investigational drug within the past 30 days
• No major surgical procedure or open biopsy within the past 28 days or anticipated need for a major surgical procedure during the course of the study