Bevacizumab and Cetuximab With or Without Irinotecan in Treating Patients With Irinotecan-Refractory Metastatic Colorectal Cancer

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