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