Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Celecoxib in Treating Patients With Stage III Colon Cancer Previously Treated With Surgery
Condition: Colorectal Cancer
MeSH terms: Colonic Neoplasms
Intervention: celecoxib; 5-fluorouracil; placebo; oxaliplatin; leucovorin
Intervention description: Patients receive celecoxib 400 mg administered by mouth, once daily.; Patients receive 400 mg/m^2 intravenous bolus then 2400 mg/m^2 continuous intravenous infusion over 46-48 hours.; Patients receive placebo administered by mouth, once daily.; Patients receive 85 mg/m^2 intravenous over two hours.; Patients receive 400 mg/m^2 intravenous over two hours.
Intervention MeSH terms: Leucovorin; Celecoxib; Fluorouracil; Oxaliplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2527.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adenocarcinoma of the colon; stage III colon cancer

Summary:

      PURPOSE: This randomized phase III trial is studying giving 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.

      RATIONALE: 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 or by stopping them from dividing. 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.
    

Eligibility criteria:

        1. Requirements for tumor parameters

               1. 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.

               2. 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.

               3. 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.

               4. No evidence of residual involved lymph node disease or metastatic disease at the
                  time of registration.

               5. 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.

          2. NSAID use

             Patients are ineligible if they plan on regular use of 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 was out period
             is required.

          3. Patient history

               1. 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.

               2. No neurosensory or neuromotor toxicity ≥ grade 2 at the time of registration.

               3. No known allergy to platinum compounds.

               4. No prior allergic reaction or hypersensitivity to sulfonamides, celecoxib or
                  NSAIDs.

               5. 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.

               6. No symptomatic pulmonary fibrosis or interstitial pneumonitis ≥ grade 2.

               7. 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.

          4. Pregancy/nursing status

             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.

          5. Age and performance status

               1. ECOG performance status 0, 1 or 2.

               2. Age at least 18 years.

          6. Required initial laboratory values

               1. Granulocytes ≥ 1,500/μL

               2. Platelet count ≥ 100,000/μL

               3. Creatinine ≤ 1.5 times upper limit of normal (ULN)

               4. Total Bilirubin ≤ 1.5 times ULN in the absence of Gilbert's disease

               5. Direct bilirubin ≤ 1.5 x upper limit of normal for patients with Gilbert's
                  syndrome