Cetuximab & Celecoxib for Metastatic Colorectal Cancer or Colorectal Cancer That Cannot Be Removed by Surgery

OBJECTIVES: Primary * Determine the time to progression in patients with unresectable or metastatic colorectal cancer treated with cetuximab and celecoxib. Secondary * Determine the response rate, median survival, and 1-year survival rate of patients treated with this regimen. * Determine the toxicity profile of this regimen in these patients. * Determine the feasibility of testing urinary PGE-M in patients treated with this regimen. * Determine the feasibility of testing serum transforming growth factor-α and amphiregulin in patients treated with this regimen. * Determine the effects of this regimen on the EGFR pathway in tumor cells (i.e., phosphorylated EGFr, phosphorylated AKT, activated mitogen-activated protein kinase). * Determine the effects of this regimen on the cyclooxygenase-2 pathway in tumor cells by measuring PGE-2 levels. OUTLINE: Patients receive cetuximab IV over 1-2 hours once weekly and oral celecoxib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Serum and urine samples are collected at baseline, after week 1, and every other course thereafter for evaluation of PGE-2 by mass spectrometry, cyclooxygenase-2 activity, and phospho-EGFR levels by western blot analysis and immunohistochemistry. Samples are also analyzed for TGF-α and amphiregulin proteomics. PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.