Cetuximab and Bevacizumab as First-Line Therapy Followed By Combination Chemotherapy and Bevacizumab With or Without Cetuximab as Second-Line Therapy in Treating Patients With Stage IV Colorectal Cancer

OBJECTIVES: Primary * To assess the efficacy of bevacizumab and cetuximab as first-line treatment for metastatic colorectal cancer, as measured by percentage of patients who remain progression-free at 6 months. Secondary * To evaluate adverse events, confirmed response, duration of response, time to disease progression, time to treatment failure, and survival of patients treated with bevacizumab and cetuximab. * To evaluate adverse events, confirmed response, duration of response, time to disease progression, time to treatment failure, and survival of patients who are refractory to dual-agent bevacizumab and cetuximab and are subsequently treated with modified FOLFOX7 chemotherapy and bevacizumab with or without cetuximab. * To evaluate quality of life parameters in patients treated with these regimens. * To estimate the direct medical resource utilization and costs. * To assess the reliability of FDG-PET as a measurement of early treatment response, as measured by percentage of patients who are progression-free at 6 months. * To identify circulating angiogenesis biomarkers. * To assay the activity of pro-angiogenic factors in plasma angiogenic assays. OUTLINE: This is a multicenter study\*. Patients are stratified according to ECOG performance status (0-1 vs 2) and number of metastatic sites (1 vs \> 1). NOTE: \*Participating site must be PET-qualified. * First-line therapy: Patients receive bevacizumab IV over 30-90 minutes and cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients with progressive disease proceed to second-line therapy. * Second-line therapy: Patients are randomized\* to 1 of 2 treatment arms. * Arm I (modified FOLFOX7 with bevacizumab only): Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. * Arm II (modified FOLFOX7 with bevacizumab and cetuximab): Patients receive bevacizumab and modified FOLFOX7 as in arm I. Patients also receive cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. NOTE: \*Randomization occurs prior to receiving first-line therapy. Patients undergo blood sample collection periodically for translational studies. Samples are analyzed for circulating endothelial cells and endothelial progenitor cells via flow cytometry; angiogenic activity of serum/plasma in angiogenesis-dependent diseases via endothelial proliferation assay and matrigel tube formation assay; and circulating angiogenesis biomarkers (i.e., free VEGF, soluble FLT-1, and KDR) via ELISA. Quality of life is assessed periodically using the UNISCALE, Skindex-16, and Skin Assessment Questionnaires. After completion of study treatment, patients are followed every 6 months for up to 3 years.