Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer

• Disease-free survival, defined as the time from surgery until the time to tumor recurrence of death, whichever is first [ Time Frame: At 5 years ] [ Designated as safety issue: No ]
  Estimated by the method of Kaplan and Meier.
  
  

• Comparison of disease free survival between arms [ Time Frame: From surgery until the time to tumor recurrence of death, whichever is first, assessed up to 8 years ] [ Designated as safety issue: No ]
  Estimated by the method of Kaplan and Meier.
  
  
• Overall survival [ Time Frame: From randomization to death, from any cause, assessed up to 8 years ] [ Designated as safety issue: No ]
  Estimated by the method of Kaplan and Meier.
  
  
• Toxicity based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Assessed up to 8 years ] [ Designated as safety issue: Yes ]
  Calculated separately for each drug within a regimen, both by course and over the entire course of therapy.
  
  

PRIMARY OBJECTIVES:

I. Compare the disease-free survival of patients with curatively resected stage III colon cancer treated with adjuvant irinotecan (irinotecan hydrochloride) vs oxaliplatin with fluorouracil and leucovorin calcium vs both regimens given consecutively (all irinotecan-containing treatment arms are closed to accrual as of 6/1/2005).

II. Compare the disease-free survival of patients treated with these regimens with vs without cetuximab.

SECONDARY OBJECTIVES:

I. Compare the overall survival of patients treated with these regimens. II. Compare the disease-free and overall survival of patients whose tumors express epidermal growth factor receptor treated with these regimens.

III. Compare the toxic effects of these regimens in these patients. IV. Compare the quality of life, measures of patient satisfaction, nutrition, and cancer risk in patients treated with these regimens.

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).

ARM I: 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 II (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 I. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

ARM III (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 I for 6 courses followed by the same treatment as in arm II for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease.

ARM IV: Patients receive cetuximab* IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

ARM V (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm IV for remainder of therapy): Patients receive cetuximab* as in arm IV and irinotecan hydrochloride, leucovorin calcium, and fluorouracil as in arm II. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

ARM VI (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm IV for remainder of therapy): Patients receive cetuximab* as in arm IV and chemotherapy as in arm III.

NOTE: *Cetuximab is administered over 2 hours at a higher dose on day 1 of course 1 only.

Quality of life is assessed at baseline, before course 6, and at the end of therapy. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 3 years.