Combination Chemotherapy and Cetuximab or Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

PRIMARY OBJECTIVES: I. To evaluate the feasibility, as defined by completion of three specific marker assays and generation of clinically meaningful endpoints, of selecting treatment regimen components based on biologic tumor characteristics in chemotherapy-naïve patients with metastatic colorectal cancer. SECONDARY OBJECTIVES: I. To investigate the response rate associated with genotype/phenotype guided therapy using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. II. To investigate the time to failure of treatment strategy associated with genotype/phenotype guided therapy, defined as the time from initiation of investigational treatment strategy until death, disease progression, initiation of a new therapeutic agent, or disease progression while on a partial or complete treatment holiday. III. To investigate the progression-free survival associated with genotype/phenotype guided therapy, defined as the time from enrollment to time of progression of disease or death. OUTLINE: Patients are assigned to treatment groups based on marker assay results. ARM A: TP-/uncertain, KRAS and BRAF wild-type, ERCC1 high ARM B: TP-/uncertain, KRAS and BRAF wild-type, ERCC1 low/uncertain ARM C: TP-/uncertain, KRAS or BRAF mutant/uncertain, ERCC1 high ARM D: TP-/uncertain, KRAS or BRAF mutant/uncertain, ERCC1 low/uncertain ARM E: TP+, KRAS and BRAF wild-type, ERCC1 high ARM F: TP+, KRAS and BRAF wild-type, ERCC1 low/uncertain ARM G: TP+, KRAS or BRAF mutant/uncertain, ERCC1 high ARM H: TP+, KRAS or BRAF mutant/uncertain, ERCC1 low/uncertain ARM I: TP uninterpretable, KRAS or BRAF uninterpretable, ERCC1 uninterpretable KRAS testing is standard of care in patients with metastatic colorectal cancer; tymidine phosphorylase, ERCC1 and BRAF testing assays are still experimental. Courses in arms A-D and arm I repeat every 28 days and courses in arms E-H repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 18 months.