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Eligibility
for people ages 18 years and up
Location
at San Francisco, California and other locations
Dates
study started
Principal Investigator

Description

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.

Official Title

A Phase III Trial of 6 Versus 12 Treatments of Adjuvant FOLFOX Plus Celecoxib or Placebo for Patients With Resected Stage III Colon Cancer

Details

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. Please see the "Arms" section for more information. 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. The primary and secondary objectives for the research study are described below.

Primary objective:

  1. 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.

Secondary objectives:

  1. 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.
  2. 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.
  3. 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 or 12 treatments of adjuvant FOLFOX chemotherapy.
  4. To assess toxicities of celecoxib as maintenance adjuvant therapy in patients with stage III colon cancer.
  5. To assess differences in cardiovascular-specific events with celecoxib versus placebo in a population of stage III colon cancer survivors.
  6. 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.

After completion of study therapy, patients are followed up every 6 months for up to 6 years.

Keywords

Colorectal Cancer adenocarcinoma of the colon stage III colon cancer Fluorouracil Oxaliplatin Celecoxib

Eligibility

For people ages 18 years and up

  1. Requirements for tumor parameters
  2. 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.
  3. 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.
  4. 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.
  5. No evidence of residual involved lymph node disease or metastatic disease at the time of registration.
  6. 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.
  7. 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.

  8. Patient history
  9. 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.
  10. No neurosensory or neuromotor toxicity ≥ grade 2 at the time of registration.
  11. No known allergy to platinum compounds.
  12. No prior allergic reaction or hypersensitivity to sulfonamides, celecoxib or NSAIDs.
  13. 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.
  14. No symptomatic pulmonary fibrosis or interstitial pneumonitis ≥ grade 2.
  15. 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.
  16. 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.

  17. Age and performance status
  18. ECOG performance status 0, 1 or 2.
  19. Age at least 18 years.
  20. Required initial laboratory values
  21. Granulocytes ≥ 1,500/μL
  22. Platelet count ≥ 100,000/μL
  23. Creatinine ≤ 1.5 times upper limit of normal (ULN)
  24. Total Bilirubin ≤ 1.5 times ULN in the absence of Gilbert's disease
  25. Direct bilirubin ≤ 1.5 x upper limit of normal for patients with Gilbert's syndrome

Locations

  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California, 95603, USA
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, 94704, USA
  • Mills-Peninsula Hospitals
    Burlingame, California, 94010, USA
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California, 95682, USA
  • John Muir Medical Center-Concord
    Concord, California, 95420, USA
  • Sutter Davis Hospital
    Davis, California, 95616, USA
  • Epic Care-Dublin
    Dublin, California, 94568, USA
  • Bay Area Breast Surgeons Inc
    Emeryville, California, 94608, USA
  • Epic Care Partners in Cancer Care
    Emeryville, California, 94608, USA
  • Marin Cancer Care Inc
    Greenbrae, California, 94904, USA
  • Marin General Hospital
    Greenbrae, California, 94904, USA
  • Contra Costa Regional Medical Center
    Martinez, California, 94553, USA
  • Memorial Medical Center
    Modesto, California, 95355, USA
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California, 94040, USA
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California, 94040, USA
  • Sutter Cancer Research Consortium
    Novato, California, 94945, USA
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, USA
  • Bay Area Tumor Institute
    Oakland, California, 94609, USA
  • Hematology and Oncology Associates-Oakland
    Oakland, California, 94609, USA
  • Stanford Cancer Institute
    Palo Alto, California, 94304, USA
  • Valley Medical Oncology Consultants
    Pleasanton, California, 94588, USA
  • Kaiser Permanente-Redwood City
    Redwood City, California, 94063, USA
  • Kaiser Permanente-Richmond
    Richmond, California, 94801, USA
  • Kaiser Permanente-Roseville
    Roseville, California, 95661, USA
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California, 95661, USA
  • Sutter Roseville Medical Center
    Roseville, California, 95661, USA
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, USA
  • Sutter General Hospital
    Sacremento, California, 95816, USA
  • Saint Helena Hospital
    Saint Helena, California, 95474, USA
  • Kaiser Permanente-San Francisco
    San Francisco, California, 94115, USA
  • California Pacific Medical Center-Pacific Campus
    San Francisco, California, 94118, USA
  • Veterans Affairs Medical Center-San Francisco
    San Francisco, California, 94121, USA
  • Kaiser Permanente-Santa Teresa-San Jose
    San Jose, California, 95119, USA
  • Santa Clara Valley Medical Center
    San Jose, California, 95128, USA
  • Kaiser Permanente San Leandro
    San Leandro, California, 94577, USA
  • Kaiser Permanente-San Rafael
    San Rafael, California, 94903, USA
  • Kaiser Permanente Medical Center-Santa Clara
    Santa Clara, California, 95051, USA
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California, 95065, USA
  • Kaiser Permanente-Santa Rosa
    Santa Rosa, California, 95403, USA
  • Sutter Pacific Medical Foundation
    Santa Rosa, California, 95403, USA
  • Kaiser Permanente-South San Francisco
    South San Francisco, California, 94080, USA
  • Kaiser Permanente-Stockton
    Stockton, California, 95210, USA
  • Palo Alto Medical Foundation-Sunnyvale
    Sunnyvale, California, 94806, USA
  • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    Vacaville, California, 95687, USA
  • Kaiser Permanente Medical Center-Vacaville
    Vacaville, California, 95688, USA
  • Kaiser Permanente-Vallejo
    Vallejo, California, 94589, USA
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California, 94589, USA
  • Kaiser Permanente-Walnut Creek
    Walnut Creek, California, 94596, USA
  • John Muir Medical Center-Walnut Creek
    Walnut Creek, California, 94598, USA
  • Providence Saint Joseph Medical Center-Disney Family Cancer Center
    Burbank, California, 91505, USA
  • City of Hope Comprehensive Cancer Center
    Duarte, California, 91010, USA
  • Comprehensive Cancer Care and Research Institute of Colorado LLC
    Englewood, California, 80113, USA
  • University Oncology Associates
    Fresno, California, 93701, USA
  • California Cancer Center - North Fresno
    Fresno, California, 93720, USA
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, 90027, USA
  • USC/Norris Comprehensive Cancer Center
    Los Angeles, California, 90033, USA
  • Los Angeles County-USC Medical Center
    Los Angeles, California, 90033, USA
  • Saint Joseph Hospital - Orange
    Orange, California, 92868, USA
  • UC Irvine Health-Chao Family Comprehensive Cancer Center
    Orange, California, 92868, USA
  • Desert Regional Medical Center
    Palm Springs, California, 92262, USA
  • Palchak David MD
    Pismo Beach, California, 93449, USA
  • Kaiser Permanente-Riverside
    Riverside, California, 92505, USA
  • Salinas Valley Memorial Hospital
    Salinas, California, 93901, USA
  • Salinas Valley Memorial
    Salinas, California, 93901, USA
  • Kaiser Permanente-San Diego Zion
    San Diego, California, 92120, USA
  • Naval Medical Center-San Diego
    San Diego, California, 92134, USA

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Alliance for Clinical Trials in Oncology
ID
NCT01150045
Phase
Phase 3
Lead Scientist
Alan Venook
Study Type
Interventional
Last Updated
June 2016