Trial Information

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. 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.