Title A Phase III Trial of 6 Versus 12 Treatments of Adjuvant FOLFOX Plus Celecoxib or Placebo for Patients with Resected State III Colon Cancer
IRB CALGB 80702
Hospital Beachwood, Fairview, Hillcrest, Independence, Main Campus, Mansfield, North Coast Cancer, South Pointe, Wooster
Stage Stage 3
Phase Phase 3
Drug Celecoxib , Fluorouracil, Leucovorin (Folinic Acid), Oxaliplatin
- To compare disease free survival of patients with stage III colon cancer randomized to standard chemotherapy only (FOLFOX) or standard chemotherapy (FOLFOX) with 3 years of celecoxib 400 mg daily.
- To contribute to an international prospective pooled analysis that will compare disease-free survival of patients with stage III colon cancer randomized to 6 treatments of adjuvant FOLFOX chemotherapy or 12 treatments of adjuvant FOLFOX chemotherapy.
- To compare overall survival of patients with stage III colon cancer randomized to standard chemotherapy only (FOLFOX) or standard chemotherapy (FOLFOX) with 3 years of celecoxib 400 mg daily.
- To contribute to an international prospective pooled analysis that will compare overall survival of patients with stage III colon cancer randomized to 6 treatments of adjuvant FOLFOX chemotherapy or 12 treatments of adjuvant FOLFOX chemotherapy.
- To assess toxicities of celecoxib as maintenance adjuvant therapy in patients with stage III colon cancer.
- To assess differences in cardiovascular-specific events with celecoxib versus placebo in a population of stage III colon cancer survivors.
- To evaluate differences in toxicities, particularly cumulative peripheral neuropathy, for patients treated with 6 treatments of FOLFOX compared to those treated with 12 treatments of FOLFOX.
- See Appendices III, IV, and V for substudy objectives.
- Histologically documented adenocarcinoma of the colon. The gross inferior (caudad) margin of the primary tumor must be at least 12 centimeters from the anal verge (i.e.. patients with rectal cancer are not eligible).
- Tumors must have been completely resected. Surgeon confirmation that the entire tumor was above the peritoneal reflection is only required in cases where it is important to establish if the tumor is a rectal or colon primary. In patients with tumor adherent to adjacent structures, en bloc Ro resection must be documented in the operative report. Treatment must begin no less than 21 days and no more than 56 days after definitive surgical resection of the primary tumor.
- Node positive disease (N1 or N2) as designated in AJCC version 7. Either at least one pathologically confirmed positive lymph node or N1C (defined as tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional lymph node metastases). Patients with resected stage IV disease are not eligible.
- No evidence of residual involved lymph node disease or metastatic disease at the time of registration.
- Patients with synchronous colon cancers are eligible and staging for stratification will be based on higher N stage of the more advanced primary tumor. However, patients with synchronous colon and rectal primary tumors are not eligible.
- Patients are ineligible if they use NSAIDs at any dose or aspirin at more than 325 mg at least three tunes per week. on average. Low-dose aspirin not exceeding 100 mg/day is permitted.
- No previous or concurrent malignancy, except treated basal cell or squamous cell cancer of skin, treated in situ cervical cancer, treated lobular or ductal carcinoma in situ in one breast, or any other cancer for which the patient has been disease-free for at least 5 years.
- No neurosensory or neuromotor toxicity ≥ grade 2 at the time of registration.
- No known allergy to platinum compounds.
- No prior allergic reaction or hypersensitivity to sulfonamides. celecoxib or NSAIDs.
- No history of upper gastrointestinal ulceration. bleeding. or perforation within the past 3 years.
- No symptomatic pulmonary fibrosis or interstitial pneumonitis ≥ grade 2.
- No cardiac risk factors including:
- Uncontrolled high blood pressure (systolic blood pressure > 150).
- Unstable angina.
- History of documented myocardial infarction or cerebrovascular accident.
- New York Heart Association class III or IV heart failure.
- Non-pregnant and not nursing. Men and women of childbearing potential must agree to employ adequate contraception for the duration of chemotherapy and for as many as 8 weeks after the completion of chemotherapy due to the unknown teratogenic effects of FOLFOX on the developing fetus.
- ECOG performance status 0, 1, or 2.
- Age at least 18 years.
- Required initial laboratory values:
- Granulocytes: ≥ 1,500/µL
- Platelet count: ≥ 100,000/µL
- Creatinine: ≤ 1.5 x upper limit of normal
- Bilirubin: ≤ 1.5 x upper limit of normal