Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Celecoxib in Treating Patients With Stage III Colon Cancer Previously Treated With Surgery
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Purpose
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.
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Colorectal Cancer |
Drug: celecoxib Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Other: placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Masking: Double-Blind 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 |
- Disease-free survival [ Designated as safety issue: No ]
- Recurrence-free survival [ Designated as safety issue: No ]
- Overall survival at 3 years [ Designated as safety issue: No ]
- Toxicity of celecoxib [ Designated as safety issue: Yes ]
- Cardiovascular-specific events [ Designated as safety issue: Yes ]
- Differences in toxicity, particularly cumulative peripheral neuropathy, of 6 vs 12 courses of FOLFOX [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 2500 |
| Study Start Date: | June 2010 |
| Estimated Primary Completion Date: | December 2019 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I
Patients receive oxaliplatin 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 oral celecoxib once daily on days 1-14 beginning on day 1 of course 2. Courses repeat every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.
|
Drug: celecoxib
Given orally
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
|
|
Placebo Comparator: Arm II
Patients receive FOLFOX as in arm I and oral placebo once daily on days 1-14 beginning on day 1 of course 2. Courses repeat every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.
|
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Other: placebo
Given orally
|
|
Experimental: Arm III
Patients receive FOLFOX and celecoxib as in arm I. Courses repeat every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Drug: celecoxib
Given orally
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
|
|
Placebo Comparator: Arm IV
Patients receive FOLFOX and placebo as in arm II. Courses repeat every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Other: placebo
Given orally
|
Detailed Description:
OBJECTIVES:
Primary
- To compare disease-free survival of patients with resected stage III colon cancer treated with adjuvant FOLFOX chemotherapy comprising oxaliplatin, fluorouracil, and leucovorin calcium with versus without celecoxib.
Secondary
- To contribute to an international prospective pooled analysis comparing disease-free survival of patients treated with these regimens.
- To compare overall survival at 3 years of patients treated with these regimens.
- To contribute to an international prospective pooled analysis comparing disease-free survival of patients treated with 6 versus 12 courses of FOLFOX chemotherapy.
- To assess toxicities of celecoxib as maintenance adjuvant therapy in these patients.
- To assess differences in cardiovascular-specific events in patients treated with versus without celecoxib.
- To evaluate differences in toxicities, particularly cumulative peripheral neuropathy, in patients treated with 6 versus 12 courses of FOLFOX chemotherapy.
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.
NOTE: *Patients with N1c-only disease (i.e., no positive nodes but N1c disease by AJCC 7) should be stratified to 1-3 nodes.
- Arm I: Patients receive oxaliplatin 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 oral celecoxib once daily on days 1-14 beginning on day 1 of course 2 of FOLFOX. Courses repeat every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive FOLFOX as in arm I and oral placebo once daily on days 1-14 beginning on day 1 of course 2. Courses repeat every 14 days for 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm III: Patients receive FOLFOX and celecoxib as in arm I. Courses repeat every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm IV: Patients receive FOLFOX and placebo as in arm II. Courses repeat every 14 days for 6 courses 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.
Blood and tissue samples maybe collected for biomarker analysis and pharmacogenomic studies.
After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for years 2-3, and then annually for 3 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the colon
- Stage III disease
The gross inferior (caudal) margin of the primary tumor must lie above the peritoneal reflection
- No rectal cancer
Synchronous colon cancers allowed
- No synchronous colon and rectal primary tumors
Completely resected tumor
Patients with adherent to adjacent structures, en bloc R_o resected tumor, must have it documented in the operative report
- 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
- Patients with resected stage IV disease are not eligible
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)
- No evidence of residual involved lymph node disease or metastatic disease
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Granulocyte count ≥ 1,500/μL
- Platelet count ≥ 100,000/μL
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 8 weeks after completion of chemotherapy
- No prior or concurrent malignancy except treated basal cell or squamous cell cancer of the skin, treated in situ cervical cancer, treated lobular or ductal carcinoma in situ in 1 breast, or any other cancer for which the patient has been disease-free for ≥ 5 years
- No neurosensory or neuromotor toxicity ≥ grade 2
- 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, but not limited to, any of the following:
- Uncontrolled high BP (systolic BP > 150 mm Hg)
- Unstable angina
- History of documented myocardial infarction or cerebrovascular accident
- NYHA class III-IV heart failure
- :
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
No concurrent NSAIDs ≥ 2 times per week on average or aspirin at > 325 mg ≥ 3 times per week on average
- Low-dose aspirin not exceeding 100 mg/day allowed
- Patients who agree to stop regular NSAIDs or higher-dose aspirin are eligble and no wash-out period is required
Contacts and Locations
Show 827 Study Locations| Principal Investigator: | Jeffrey A. Meyerhardt, MD, MPH | Dana-Farber Cancer Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | Monica M. Bertagnolli, Cancer and Leukemia Group B |
| ClinicalTrials.gov Identifier: | NCT01150045 History of Changes |
| Other Study ID Numbers: | CDR0000675693, CALGB-80702 |
| Study First Received: | June 23, 2010 |
| Last Updated: | February 17, 2013 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
adenocarcinoma of the colon stage III colon cancer |
Additional relevant MeSH terms:
|
Colonic Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Calcium, Dietary Fluorouracil Oxaliplatin |
Leucovorin Levoleucovorin Celecoxib Bone Density Conservation Agents Physiological Effects of Drugs Pharmacologic Actions Antimetabolites Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Vitamin B Complex Vitamins |
ClinicalTrials.gov processed this record on May 19, 2013