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Oxaliplatin, Leucovorin Calcium, and Fluorouracil with or without Celecoxib in Treating Patients with Stage III Colon Cancer Previously Treated with Surgery
Trial Status: closed to accrual and intervention
This phase III trial studies oxaliplatin, leucovorin calcium, and fluorouracil together to compare how well they work when given together with or without celecoxib in treating patients with stage III colon cancer previously treated with surgery. Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving oxaliplatin, leucovorin calcium, and fluorouracil is more effective with or without celecoxib in treating colon cancer.
Inclusion Criteria
Histologically documented adenocarcinoma of the colon; the gross inferior (caudad) margin of the primary tumor must lie above the peritoneal reflection (i.e., patients with rectal cancer are not eligible); 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
Tumors must have been completely resected; in patients with tumor adherent to adjacent structures, en bloc R0 resection must be documented in the operative report or otherwise confirmed by the surgeon; near or positive radial margin are NOT exclusions as long as en bloc resection was performed; positive proximal margin or distal margin is an exclusion
Node positive disease (N1 or N2) as designated in American Joint Committee on Cancer (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 plan on regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average; low-dose aspirin not exceeding 100 mg/day is permitted; patients who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out period is required
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, upper gastrointestinal bleeding, or upper gastrointestinal perforation within the past 3 years; patients with ulceration, bleeding or perforation in the lower bowel are NOT excluded
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
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
Granulocytes >= 1,500/uL
Platelet count >= 100,000/uL
Creatinine =< 1.5 x upper limit of normal
Total bilirubin =< 1.5 x upper limit of normal in the absence of Gilbert’s disease; for patients with Gilbert’s syndrome: direct bilirubin =< 1.5 x upper limit of normal
Additional locations may be listed on ClinicalTrials.gov for NCT01150045.
I. To compare disease-free survival of patients with stage III colon cancer randomized to standard chemotherapy only (oxaliplatin, fluorouracil, and leucovorin calcium [FOLFOX]) or standard chemotherapy (FOLFOX) with 3 years of celecoxib 400 mg daily.
SECONDARY OBJECTIVES:
I. 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.
II. 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.
III. 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.
IV. To assess toxicities of celecoxib as maintenance adjuvant therapy in patients with stage III colon cancer.
V. To assess differences in cardiovascular-specific events with celecoxib versus placebo in a population of stage III colon cancer survivors.
VI. 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.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM A: Patients receive oxaliplatin intravenously (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 placebo orally (PO) once daily (QD). Cycles repeat every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive FOLFOX as in Arm A and celecoxib PO QD. Cycles repeat every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive FOLFOX and placebo as in Arm A. Cycles repeat every 14 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
ARM D: Patients receive FOLFOX and celecoxib as in Arm B. Cycles repeat every 14 days for 6 cycles 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.
After completion of study treatment, patients are followed up every 6 months for 6 years.
Trial PhasePhase III
Trial Typetreatment
Lead OrganizationAlliance for Clinical Trials in Oncology
