Celecoxib in Preventing Polyps in Patients Who Have Undergone Surgery for Stage I Colon Cancer

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. It is not yet known whether celecoxib is effective in preventing polyps in patients with colon cancer. PURPOSE: Randomized phase III trial to study the effectiveness of celecoxib in preventing the development of polyps in patients who have undergone surgery for stage I colon cancer.

Detailed Description
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OBJECTIVES: Primary Compare celecoxib vs placebo, in terms of decreasing the incidence of adenomatous polyps of the colon and rectum, in patients with resected stage I adenocarcinoma of the colon. Secondary Compare disease-free survival of patients treated with these regimens. Compare the effect of these regimens on self-reported symptoms and health-related quality of life of these patients. Compare the quality of life of patients treated with these regimens. Compare the benefits of celecoxib in patients with primary tumors or polyps that express cyclo-oxygenase-2 (COX-2) with those that do not express COX-2. Compare the expression of signaling targets such as serine/threonine AKT, extracellular signal-regulated kinase 2 (ERK2), and endoplasmic reticulum Ca+2- ATPases in the index tumor and polyps. Determine the toxicity and safety of celecoxib in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to gender, tumor stage (T1 vs T2), age (≤ 49 vs 50 to 59 vs ≥ 60 years), and current aspirin use (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral celecoxib twice daily for 3 years. Arm II: Patients receive oral placebo twice daily for 3 years. In both arms, treatment continues in the absence of unacceptable toxicity or the diagnosis of invasive colon cancer, carcinoma in situ of the colon or rectum, or a non-colon primary cancer. Quality of life is assessed at baseline and then at 6, 12, 24, 36, and 42 months. Patients are followed at 6 months and at 2 years. PROJECTED ACCRUAL: A total of 1,200 patients (600 per treatment arm) will be accrued for this study within 2.5 years.

Official Title
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Celecoxib Polyp Prevention Trial in Participants With Resected Stage I Colon Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Celecoxib
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon Stage I disease Distal border of tumor ≥ 12 cm from the anal verge Tumor completely resected within the past 90 days Must have undergone a preoperative or postoperative colonoscopy to the cecum (or small bowel anastomosis) within the past 90 days All observed polyps must have been removed Patients with a history suggestive of hereditary non-polyposis colorectal cancer (HNPCC) must have a normal microsatellite instability status by immunohistochemistry or polymerase chain reaction Patients with family history of colon cancer who have not been diagnosed with HNPCC are eligible No prior familial adenomatous polyposis No prior invasive cancer or carcinoma in situ of the colon or rectum No clinical or radiologic evidence of metastatic disease PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy At least 10 years Hematopoietic Complete blood count normal Platelet count normal Hepatic Aspartate aminotransferase (AST) normal Bilirubin normal Alkaline phosphatase normal Renal Creatinine normal Cardiovascular No active ischemic heart disease No New York Heart Association class III or IV heart disease No myocardial infarction within the past 6 months No symptomatic arrhythmia No symptomatic peripheral vascular disease or carotid disease that would preclude study participation Pulmonary No aspirin-sensitive asthma Gastrointestinal No history of inflammatory bowel disease No history of upper gastrointestinal bleeding No history of duodenal or gastric ulcer Other No known hypersensitivity to any COX-2 inhibitor, NSAIDs, aspirin, or sulfonamides No non-colorectal malignancy within the past 5 years except carcinoma in situ of the cervix, melanoma in situ, or basal cell or squamous cell skin cancer No other disease that would preclude study participation No psychiatric disorders, including history of clinical depression or addictive disorders, that would preclude giving informed consent or long-term compliance No rheumatologic or skeletal disorders requiring chronic NSAIDs or steroid therapy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy Not specified Surgery See Disease Characteristics Other No other concurrent investigational agents for colon cancer No concurrent chronic use of other cyclo-oxygenase-2 (COX-2) inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), or salicylates (e.g., aspirin) Chronic use is defined as use for more than an average of 3 days per month Concurrent NSAIDs allowed for up to 10 consecutive days for temporary relief due to inflammatory syndromes, injury, or postoperative pain Cardioprotective doses of aspirin (≤ 81 mg/day or 325 mg every other day) allowed No concurrent fluconazole or lithium

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1: placebo<br>one placebo capsule taken orally twice a day for 3 years | Drug: Celecoxib<br> <br> * Other names: Celebrex;|
| Experimental: Arm 2: celecoxib<br>one 400 mg capsule taken orally twice a day for 3 years | Other: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine whether celecoxib 400 mg bid for 3 years will decrease the incidence of adenomatous polyps of the colon and rectum in participants with Stage I adenocarcinoma of the colon. |  | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To access whether celecoxib will increase disease-free survival. |  | 60 months | 
| To access whether celecoxib therapy affects self-reported symptoms and health-related quality of life. |  | 60 months | 
| To describe the quality of life in early stage colon cancer patients. |  | 42 months | 
| To evaluate if the benefits from celecoxib are more pronounced in a cohort of participants whose primary colon tumors and polyps express COX-2. |  | 60 months | 
| To examine the expression of signaling targets such as serine/threonine kinase (AKT) extracellular signal-regulated kinase (ERK2), and endoplasmic reticulum Ca2+-ATPases in the index tumor and polyps. |  | 60 months | 
| To monitor the toxicity and safety of celecoxib in this population. |  | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the colon, stage I colon cancer