RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Celecoxib and selenium may be effective in preventing the recurrence of adenomatous colorectal polyps. It is not yet known whether combining celecoxib with selenium is more effective than either celecoxib or selenium alone in preventing the recurrence of adenomatous colorectal polyps.

PURPOSE: This randomized phase III trial is studying celecoxib and selenium to see how well they work compared to either celecoxib or selenium alone in preventing the recurrence of polyps in patients with adenomatous colorectal polyps.

Condition	Treatment or Intervention	Phase
Colon Cancer Rectal Cancer	Drug: celecoxib  Drug: selenium  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the effects of celecoxib vs selenium vs the combination of celecoxib and selenium vs placebo on the recurrence of adenomatous colorectal polyps, in terms of histologic type, number, size, and location, in patients with adenomatous colorectal polyps.
• Compare the effect of these regimens on carcinogenesis, in terms of gene methylation patterns and cyclo-oxygenase expression, in these patients.
• Compare the type, incidence, and outcome of side effects in patients treated with these regimens.
• Determine patient adherence to long-term treatment with these regimens.
• Determine whether adherence to protocol procedures, dietary intake, smoking history, medication intake, and physical activity in these patients affects the relationships of these regimens to this study.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to use of low-dose (≤ 81 mg/day) aspirin (yes vs no). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive oral celecoxib and oral selenium once daily.
• Arm II: Patients receive oral celecoxib and oral placebo once daily.
• Arm III: Patients receive oral selenium and oral placebo once daily.
• Arm IV: Patients receive oral placebo once daily. In all arms, treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

Patients undergo follow-up colonoscopy 2.5-5 years after baseline colonoscopy.

PROJECTED ACCRUAL: A total of 1,600 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  40 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenomatous polyps
• Meets the following criteria by colonoscopy (performed within the past 6 months):
• Cecum was totally visualized or reached
• At least 90% visualization of colon surface area
• Removed at least 1 adenomatous polyp of at least 3 mm in size during procedure
• Removed no more than 10 adenomatous polyps of any size by endoscopy
• All other neoplastic and non-neoplastic colon polyps must have been completely removed (except for diminutive [less than 3 mm] sessile rectal polyps)
• No prior diagnosis of any of the following:
• Colorectal cancer
• Familial adenomatous polyposis
• Ulcerative colitis
• Crohn's disease
• Hereditary non-polyposis colon cancer (HNPCC), defined as:
• Histologically confirmed colorectal cancer in at least 3 relatives, 1 of whom is a first-degree relative of the other 2
• Disease occurrence in at least 2 consecutive generations
• Colorectal cancer diagnosis in at least 1 family member who is less than 50 years of age
• Patients with a family history of colorectal cancer but who are not diagnosed with HNPCC are allowed
• No more than 1 prior segmental colon resection

PATIENT CHARACTERISTICS: Age

• 40 to 80

Performance status

• SWOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Hemoglobin > 11 g/dL
• WBC 3,000 - 11,000/mm^3

Hepatic

• AST and ALT < 2 times upper limit of normal
• Bilirubin < 2.0 mg/dL

Renal

• Creatinine < 1.9 mg/dL
• Creatinine clearance ≥ 25% of normal

Cardiovascular

• No unstable* cardiac disease despite medication (e.g., diuretics or digitalis)
• No uncontrolled hypertension (i.e., systolic blood pressure ≥ 170 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg) despite medication NOTE: *Unstable defined as unable to walk across the room without chest pain or shortness of breath

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception for at least 2 months before and during study treatment
• Resident of a clinical center metropolitan area or obtaining regular health care in a clinical metropolitan area for at least 6 months out of the year
• Must be able to swallow pills
• No substantially worsened asthma secondary to aspirin or other NSAIDs requiring hospitalization or an emergency room visit
• No unexpected weight loss of 10% or more within the past 6 months
• No prior rheumatoid arthritis
• No poorly controlled diabetes mellitus despite medication, defined as:
• Blood sugar level ≥ 200 mg/dL on more than half of the readings taken within the past month
• No prior anaphylactic reaction to aspirin, other NSAIDs, or sulfa drugs, such as the following:
• Thickening of the tongue requiring steroids
• Drop in blood pressure requiring medication or hospitalization
• Shortness of breath requiring oxygen
• Hives
• Rash
• No invasive malignancy within the past 5 years that required medical excision, radiotherapy, or chemotherapy except basal cell or squamous cell carcinoma

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent drugs that regulate the immune system

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• No concurrent prednisone > 10 mg/day

Radiotherapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 1 month since prior fluconazole
• Prior enrollment in another adenoma prevention study allowed
• Concurrent routine aspirin (≤ 81 mg/day) allowed
• No concurrent fluconazole
• No concurrent lithium
• No regular use of non-steroidal anti-inflammatory drugs (NSAIDs)
• No concurrent enrollment in another research study using pharmacological cancer drugs, a cyclo-oxygenase-2 inhibitor, or selenium
• No other concurrent selenium unless dosage is ≤ 50 µg/day

Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, TUSCON,  Arizona,  85724,  United States; Recruiting
      Mayo Clinic Scottsdale, Scottsdale,  Arizona,  85259,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
Texas
      Baylor University Medical Center, Dallas,  Texas,  75246,  United States; Recruiting

Study chairs or principal investigators

M. Peter Lance, MD,  Principal Investigator,  Arizona Cancer Center   

Study ID Numbers:  CDR0000353185; UARIZ-HSC-00142; NCT00078897
Record last reviewed:  April 2004
Last Updated:  March 10, 2005
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00078897
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08