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

Brief Summary

Detailed Description

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.

Primary Outcomes