Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Celecoxib in Treating Patients With Stage III Colon Cancer Previously Treated With Surgery

• Disease-free survival [ Designated as safety issue: No ]
  

• Recurrence-free survival [ Designated as safety issue: No ]
  
• Overall survival at 3 years [ Designated as safety issue: No ]
  
• Toxicity of celecoxib [ Designated as safety issue: Yes ]
  
• Cardiovascular-specific events [ Designated as safety issue: Yes ]
  
• Differences in toxicity, particularly cumulative peripheral neuropathy, of 6 vs 12 courses of FOLFOX [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• To compare disease-free survival of patients with resected stage III colon cancer treated with adjuvant FOLFOX chemotherapy comprising oxaliplatin, fluorouracil, and leucovorin calcium with versus without celecoxib.

Secondary

• To contribute to an international prospective pooled analysis comparing disease-free survival of patients treated with these regimens.
• To compare overall survival at 3 years of patients treated with these regimens.
• To contribute to an international prospective pooled analysis comparing disease-free survival of patients treated with 6 versus 12 courses of FOLFOX chemotherapy.
• To assess toxicities of celecoxib as maintenance adjuvant therapy in these patients.
• To assess differences in cardiovascular-specific events in patients treated with versus without celecoxib.
• To evaluate differences in toxicities, particularly cumulative peripheral neuropathy, in patients treated with 6 versus 12 courses of FOLFOX chemotherapy.

OUTLINE: This is a multicenter study. Patients are stratified according to number of positive lymph nodes* (1-3 vs 4 or more) and concurrent regular low-dose of aspirin (yes vs no). Patients are randomized to 1 of 4 treatment arms.

NOTE: *Patients with N1c-only disease (i.e., no positive nodes but N1c disease by AJCC 7) should be stratified to 1-3 nodes.

• Arm I: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours (FOLFOX) on day 1. Patients also receive oral celecoxib once daily on days 1-14 beginning on day 1 of course 2 of FOLFOX. Courses repeat every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive FOLFOX as in arm I and oral placebo once daily on days 1-14 beginning on day 1 of course 2. Courses repeat every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.
• Arm III: Patients receive FOLFOX and celecoxib as in arm I. Courses repeat every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm IV: Patients receive FOLFOX and placebo as in arm II. Courses repeat every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

In all arms, treatment with celecoxib or placebo continues for 3 years in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples maybe collected for biomarker analysis and pharmacogenomic studies.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for years 2-3, and then annually for 3 years.