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

You may be eligible if

• 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