Selenium for Prevention of Adenomatous Colorectal Polyps

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 or recurrence of cancer. Selenium may be effective in preventing the recurrence of adenomatous colorectal polyps. PURPOSE: This randomized phase III trial is studying selenium to see how well it works in preventing the recurrence of polyps in patients with adenomatous colorectal polyps.

Detailed Description
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OBJECTIVES: Primary Compare the effects of selenium vs placebo on the recurrence of adenomatous colorectal polyps, in terms of histologic type, degree of dysplasia, number, size, and location, in patients with adenomatous colorectal polyps. 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. Secondary Determine the effects of regimen modification by baseline blood selenium level, low-dose aspirin, selenoprotein genetic marker polymorphisms (e.g., GPx-1, GPx-2, and SEP15) Determine the effects of low-dose aspirin (81 mg/day) modification by ornithine decarboxylase promoter genotype, and toxicity by slow-metabolizer genotypes of the cytochrome p450 2C9 and UT1A6 loci in these patients. 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 2 treatment arms. Arm I: Patients receive oral selenium once daily. Arm II: Patients receive oral placebo once daily. In both arms, treatment continues for up to 5 years* in the absence of disease progression or unacceptable toxicity. Patients undergo follow-up colonoscopy approximately 5 years* after baseline colonoscopy. NOTE: Some patients will continue participation for up to 7 and a half years PROJECTED ACCRUAL: A total of 1,600 patients with an adenoma will be randomized to this study, followed by a second group of randomization of 200 patients with at least one advanced adenoma (at baseline) for a substudy. Total planned randomizations = 1,800 participants.

Official Title
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Phase III Study of the Effects of Selenium on Adenomatous Polyp Recurrence

Conditions
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Colorectal Cancer, Adenomatous Colorectal Polyps, Precancerous Condition

Intervention / Treatment
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* Drug: Selenium


Participation Criteria
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Eligibility Criteria
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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 (For the Advanced Adenoma Sub-study: Removal of at least 1 advanced colorectal adenomatous polyp during procedure. An adenoma is considered advanced if it is 10 mm or greater in size, and/or has villous histology and/or shows high grade dysplasia) 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) For the sub-study, at least 1 advanced adenomatous polyp defined as 10 mm or greater in size and/or has villous histology and/or shows high grade dysplasia 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 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 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 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 Not specified Radiotherapy No concurrent radiotherapy Surgery See Disease Characteristics Other Prior enrollment in another adenoma prevention study allowed Concurrent routine aspirin (≤ 81 mg/day) allowed 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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Selenium<br>Participants receive oral selenium 200 mcg once daily. | Drug: Selenium<br>* Participants will be randomized either to selenium or placebo, taking the randomized intervention for 3 to 5 years, depending on when their recommended follow up colonoscopy is scheduled.<br>* Other names: SelenoExcell;|
| Placebo Comparator: Placebo<br>Participants receive oral placebo once daily. | Drug: Selenium<br>* Participants will be randomized either to selenium or placebo, taking the randomized intervention for 3 to 5 years, depending on when their recommended follow up colonoscopy is scheduled.<br>* Other names: SelenoExcell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Recurrent Adenomas at Surveillance Colonoscopy | Detection of metachronous colorectal adenomas during follow-up, by treatment, in the original cohort. Surveillance colonoscopy is recommended 3 to 5 years after removal of colorectal adenoma(s). Participants will remain on the study intervention until their surveillance colonoscopy. Surveillance colonoscopy is determined by participants' GI physician. | 3 to 5 years after baseline colonoscopy | 
| Median Selenium Blood Levels at One Year. | Adequate adherence to long-term selenium treatment as measured by blood selenium levels (ng/mL) at one year. | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colon cancer, rectal cancer, colorectal cancer, adenomatous polyp