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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01150045
Recruitment Status : Unknown
Verified March 2022 by Alliance for Clinical Trials in Oncology.
Recruitment status was:  Active, not recruiting
First Posted : June 24, 2010
Results First Posted : August 6, 2021
Last Update Posted : March 22, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Drug: celecoxib Drug: 5-fluorouracil Other: placebo Drug: oxaliplatin Drug: leucovorin Phase 3

Detailed Description:

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2527 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Study Start Date : June 2010
Actual Primary Completion Date : February 28, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm A - FOLFOX and placebo (12 treatments)
Patients receive FOLFOX every 2 weeks plus placebo every day for 12 treatments (24 weeks). Each 2-week period is called a cycle. FOLFOX includes oxaliplatin, leucovorin and 5-FU.Then, patients receive placebo alone every day for 3 years total.
 Drug: 5-fluorouracil
Patients receive 400 mg/m^2 intravenous bolus then 2400 mg/m^2 continuous intravenous infusion over 46-48 hours.

Other: placebo
Patients receive placebo administered by mouth, once daily.

Drug: oxaliplatin
Patients receive 85 mg/m^2 intravenous over two hours.

Drug: leucovorin
Patients receive 400 mg/m^2 intravenous over two hours.
Experimental: Arm B - FOLFOX and celecoxib (12 treatments)
Patients receive FOLFOX every 2 weeks plus celecoxib every day for 12 treatments (24 weeks). Each 2-week period is called a cycle. FOLFOX includes oxaliplatin, leucovorin and 5-FU.Then, patients receive celecoxib alone every day for 3 years total.
 Drug: celecoxib
Patients receive celecoxib 400 mg administered by mouth, once daily.

Drug: 5-fluorouracil
Patients receive 400 mg/m^2 intravenous bolus then 2400 mg/m^2 continuous intravenous infusion over 46-48 hours.

Drug: oxaliplatin
Patients receive 85 mg/m^2 intravenous over two hours.

Drug: leucovorin
Patients receive 400 mg/m^2 intravenous over two hours.
Active Comparator: Arm C - FOLFOX and placebo (6 treatments)
Patients receive FOLFOX every 2 weeks plus placebo every day for 6 treatments (12 weeks). Each 2-week period is called a cycle. FOLFOX includes oxaliplatin, leucovorin and 5-FU.Then, patients receive placebo alone every day for 3 years total.
 Drug: 5-fluorouracil
Patients receive 400 mg/m^2 intravenous bolus then 2400 mg/m^2 continuous intravenous infusion over 46-48 hours.

Other: placebo
Patients receive placebo administered by mouth, once daily.

Drug: oxaliplatin
Patients receive 85 mg/m^2 intravenous over two hours.

Drug: leucovorin
Patients receive 400 mg/m^2 intravenous over two hours.
Experimental: Arm D - FOLFOX and celecoxib (6 treatments)
Patients receive FOLFOX every 2 weeks plus celecoxib every day for 6 treatments (12 weeks). Each 2-week period is called a cycle. FOLFOX includes oxaliplatin, leucovorin and 5-FU.Then, patients receive celecoxib alone every day for 3 years total.
 Drug: celecoxib
Patients receive celecoxib 400 mg administered by mouth, once daily.

Drug: 5-fluorouracil
Patients receive 400 mg/m^2 intravenous bolus then 2400 mg/m^2 continuous intravenous infusion over 46-48 hours.

Drug: oxaliplatin
Patients receive 85 mg/m^2 intravenous over two hours.

Drug: leucovorin
Patients receive 400 mg/m^2 intravenous over two hours.


Outcome Measures
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Primary Outcome Measures :
  1. Disease-free Survival [ Time Frame: At 3 years of follow-up ]
    Disease-Free Survival (DFS) is defined as the time of randomization until documented progression or death from any cause. The endpoint of this trial is to compare disease-free survival of patients with stage III colon cancer randomized to standard chemotherapy only (FOLFOX; Arm A and Arm C) or standard chemotherapy (FOLFOX) with 3 years of celecoxib 400 mg daily (Arm B and Arm D). The percentage of patients who were alive and disease free after 3 years are reported here. A log-rank test stratified with the stratification factors was used to compare disease-free survival (celecoxib vs placebo)


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: up to 3 years from registration ]
    Overall Survival (DFS) is defined as the time of randomization until documented death from any cause. The endpoint is to compare overall survival of patients with stage III colon cancer randomized to standard chemotherapy only (FOLFOX; Arm A and Arm C) or standard chemotherapy (FOLFOX) with 5 years of celecoxib 400 mg daily (Arm B and Arm D). The percentage of patients who were alive after 3 years are reported here.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01150045


Locations
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Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
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Study Chair: Jeffrey Meyerhardt, MD, MPH Dana-Farber Cancer Institute
  Study Documents (Full-Text)

Documents provided by Alliance for Clinical Trials in Oncology:
Study Protocol and Statistical Analysis Plan  [PDF] February 24, 2021

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01150045    
Other Study ID Numbers: CALGB-80702
U10CA031946 ( U.S. NIH Grant/Contract )
CALGB-80702
CDR0000675693 ( Registry Identifier: NCI Physician Data Query )
First Posted: June 24, 2010    Key Record Dates
Results First Posted: August 6, 2021
Last Update Posted: March 22, 2022
Last Verified: March 2022
Keywords provided by Alliance for Clinical Trials in Oncology:
adenocarcinoma of the colon
stage III colon cancer
Additional relevant MeSH terms:
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Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Leucovorin
Celecoxib
Fluorouracil
Oxaliplatin
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics