A Randomized Phase II Study of Bevacizumab in Combination With Cetuximab Plus Irinotecan, or in Combination With Cetuximab Alone, in Irinotecan-Refractory Colorectal Cancer

Study start date: December 1, 2003

Inclusion Criteria: * Histologically or cytologically confirmed colorectal cancer * Metastatic disease by diagnostic imaging studies * Measurable disease * At least 1 unidimensionally measurable lesion with minimum lesion size at least twice the slice thickness of the imaging study used * Refractory to irinotecan, evidenced by clinical documentation * Received at least 1 prior irinotecan-containing chemotherapy regimen for metastatic disease and progressed during or within 6 weeks after completion of therapy * Must have received prior irinotecan according to 1 of the following schedules: * Weekly administration with a starting dose of 100-125 mg/m\^2 * Biweekly administration (every other week) with a starting dose of approximately 180 mg/m\^2 * Once every three weekly administration with a starting dose of 300-350 mg/m\^2 * No known brain metastases * No prior primary CNS tumors * Performance status - ECOG 0-1 * Performance status - Karnofsky 80-100% * More than 3 months * WBC \>= 3,000/mm\^3 * Absolute neutrophil count \>= 1,500/mm\^3 * Platelet count \>= 100,000/mm\^3 * Hemoglobin \>= 9 g/dL * No bleeding diathesis or coagulopathy * Bilirubin normal * AST and ALT =\< 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of known liver metastases) * INR \< 1.5 (for patients receiving warfarin) * Creatinine =\< ULN * Creatinine clearance ≥ 60 mL/min * No proteinuria * No prior stroke * No symptomatic congestive heart failure * No unstable angina pectoris * No uncontrolled hypertension * No clinically significant cardiac arrhythmia * None of the following arterial thromboembolic events within the past 6 months: * Myocardial infarction * Cerebrovascular accident * Transient ischemic attack * Unstable angina * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 3 months after study participation * No significant traumatic injury within the past 28 days * No grade 3 or greater neurotoxicity * No uncontrolled seizures * No prior allergic reactions attributed to compounds of similar chemical or biological composition to study agents * No prior irinotecan intolerance * No ongoing or active infection requiring parenteral antibiotics * No serious nonhealing active wound, ulcer, or bone fracture * No psychiatric illness or social situation that would preclude study compliance * No other concurrent uncontrolled illness that would preclude study participation * No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies * No prior cetuximab * No other prior epidermal growth factor receptor-directed therapy * No prior anticancer murine or chimeric monoclonal antibody therapy * Prior humanized monoclonal antibody therapy allowed * No prior bevacizumab * No other prior vascular endothelial growth factor-targeted therapy * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * More than 4 weeks since prior radiotherapy * More than 28 days since prior major surgical procedure or open biopsy * Recovered from all prior therapy * Any number of prior standard or investigational regimens allowed * No other concurrent investigational agents * No other concurrent anticancer therapy * No recent or concurrent thrombolytic agents * No recent or concurrent full-dose warfarin except as required to maintain patency of preexisting, permanent indwelling IV catheters * No concurrent therapeutic heparin * Concurrent prophylactic low-molecular weight heparin allowed * No concurrent chronic daily aspirin (\> 325 mg/day) * No concurrent nonsteroidal anti-inflammatory medications known to inhibit platelet function * No concurrent combination antiretroviral therapy for HIV-positive patients