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

INCLUSION:

Metastatic or locally recurrent colorectal adenocarcinoma
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
Age 18 and over
Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Prothrombin time (PT)/international normalized ratio (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
Partial thromboplastin time (PTT) < 1.5 times upper limit of normal (ULN)
Alanine transaminase (ALT) and aspartate aminotransferase (AST) < 3 times ULN
Bilirubin ≤ 1.5 times ULN
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

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

Blood pressure < 150/90 mm Hg
Stable regimen of anti-hypertensive therapy
More than 28 days since prior major or open surgery
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

EXCLUSION:

Pregnant or nursing

Arterial thromboembolic events within the past 6 months, including the following:

Transient ischemic attack
Cerebrovascular accident
Unstable angina pectoris
Myocardial infarction
Symptomatic arrhythmia
Symptomatic congestive heart failure
Clinically significant peripheral artery disease
New York Heart Association class III or IV heart disease
Serious nonhealing wound, ulcer, or bone fracture within the past 28 days
Significant traumatic injury within the past 28 days
Neuropathy ≥ grade 2
Ongoing or active infection
Concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
Prior chemotherapy for metastatic disease. Adjuvant therapy completed at least 12 months before first evidence of metastasis allowed
Cardiovascular, renal, hepatic, or other nonmalignant systemic disease that would preclude study therapy