A Randomized Phase III Trial of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) With or Without Cetuximab (C225) After Curative Resection for Patients With Stage III Colon Cancer

PRIMARY OBJECTIVES: I. Disease-free Survival (Arms A and D: Wild-type KRAS Patients) SECONDARY OBJECTIVES: I. Disease-free Survival (Arms A and D: Mutant KRAS Patients) II. Disease-free Survival III. Overall Survival IV. Toxicity OUTLINE: This is a randomized, multicenter study. Patients are stratified according to positive lymph node involvement (1-3 vs 4 or more), histology (high \[poorly differentiated or undifferentiated\] vs low \[well to moderately differentiated\]), and clinical T stage (T1 or T2 vs T3 vs T4). Patients are randomized to 1 of 6 treatment arms (as of 6/1/2005, patients are randomized to treatment arms I and IV only; arms II, III, V, and VI are closed to accrual). As of 8/18/2008, pre-screening for KRAS status was added with mutant KRAS (or KRAS not evaluable) patients put on arm G and wild-type KRAS patients randomized between arm A and arm D. ARM A: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. ARM B (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive irinotecan hydrochloride IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. ARM C (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive the same treatment as in arm A for 6 courses followed by the same treatment as in arm B for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease. ARM D: Patients receive cetuximab\* IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. ARM E (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm D for remainder of therapy): Patients receive cetuximab\* as in arm D and irinotecan hydrochloride, leucovorin calcium, and fluorouracil as in arm B. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. ARM F (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm D for remainder of therapy): Patients receive cetuximab\* as in arm D and chemotherapy as in arm C. ARM G (added as of 8/18/2008, mutant KRAS (or KRAS not evaluable) patients): Locally directed therapy. NOTE: \*Cetuximab is administered over 2 hours at a higher dose on day 1 of course 1 only. Quality of life (QOL) is assessed at baseline, 3 months, and at the end of therapy. As of 8/18/2008, QOL was discontinued. Patients are followed for a maximum of 8 years from randomization.