Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer

DISEASE CHARACTERISTICS:

• Diagnosis of colorectal adenocarcinoma

  • Metastatic or locally recurrent disease
• Measurable disease

• At least 2 formalin-fixed paraffin embedded core needle biopsies OR fine needle aspirate containing a minimum of 3 clusters of malignant cells and fixed tissue from the previous biopsy

  • If no tissue samples are available the patient must be willing to undergo biopsy of a metastatic site

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• PT (INR) ≤ 1.5 unless patient is receiving full-dose anticoagulants AND the following criteria are met:

  • In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low molecular weight heparin
  • No active bleeding or pathological condition that is associated with a high risk of bleeding
• PTT < 1.5 times upper limit of normal (ULN)
• ALT and AST < 3 times ULN
• Bilirubin ≤ 1.5 times ULN
• No hepatic disease that would preclude study therapy

Renal

• Creatinine ≤ 1.8 mg/dL

• Meets 1 of the following criteria:

  • Protein negative on urine dipstick
  • Urine protein/creatinine ratio < 1.0
  • Less than 2 g protein on 24-hour urine collection
• No renal disease that would preclude study therapy

Cardiovascular

• No arterial thromboembolic events within the past 6 months, including the following:

  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina pectoris
  • Myocardial infarction

• Patients with a history of hypertension must meet the following criteria:

  • Blood pressure < 150/90 mm Hg
  • Stable regimen of anti-hypertensive therapy
• No symptomatic arrhythmia
• No symptomatic congestive heart failure
• No clinically significant peripheral artery disease
• No New York Heart Association class III or IV heart disease
• No other cardiovascular disease that would preclude study therapy

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

• Prior non-colorectal malignancies are allowed provided the following criteria are met:

  • No current clinical evidence of persistent or recurrent disease
  • No active therapy for non-colorectal malignancy, including hormonal therapy
• No serious nonhealing wound, ulcer, or bone fracture within the past 28 days
• No significant traumatic injury within the past 28 days
• No neuropathy ≥ grade 2
• No other nonmalignant systemic disease that would preclude study therapy
• No ongoing or active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• No prior chemotherapy for metastatic disease

  • Adjuvant therapy completed at least 12 months before first evidence of metastasis allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• More than 28 days since prior major surgery
• More than 28 days since prior open biopsy