Irinotecan Hydrochloride With FOLFIRI and Cetuximab as First-Line Therapy in Treating Patients With RAS Wild-Type Colorectal Cancer

PRIMARY OBJECTIVES: I. To define the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the phase II recommended dosage of irinotecan (irinotecan hydrochloride) administered in the FOLFIRI regimen plus cetuximab in metastatic colorectal cancer (mCRC) patients with \*1/\*1 and \*1/\*28 uridine diphosphate glucuronosyltransferase (UGT1A1) genotype treated as first line chemotherapy. SECONDARY OBJECTIVE: To estimate the response rate, progression-free survival (PFS) and metastasectomy (with curative intent) rate in the overall patient population (both genotype cohorts). OTHER OBJECTIVES: I. To evaluate the variability of irinotecan pharmacokinetics, in combination with cetuximab, in patients with \*1/\*1 and \*1/\*28 genotype and the effect of the pharmacokinetic profile on toxicity and response rate. II. To evaluate the pharmacokinetic profile of irinotecan and its major metabolites in the absence and the presence of cetuximab administration, in order to define the effect of the chimeric monoclonal antibody on irinotecan pharmacokinetics. OUTLINE: This is a dose-escalation study of irinotecan hydrochloride in patients with UGT1A1. Patients receive irinotecan hydrochloride intravenously (IV) over 1-2 hours, fluorouracil IV continuously over 46 hours, and leucovorin calcium IV on days 1 and 15. Patients also receive cetuximab IV over 2 hours on days 3 and 15 of course 1 and days 1 and 15 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.