CALCIUM AND ASPIRIN PREVENTION TRIAL

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DESCRIPTION (Adapted from the investigator's abstract): Modification of the carcinogenic process by dietary supplements and pharmacologic agents is a major emphasis in colon cancer prevention research. Two sequential studies are proposed to investigate the role of combined calcium and aspirin supplementation in colon cancer chemoprevention. The two agents are chosen because (a) extensive epidemiologic and laboratory data support their chemopreventive potential, (b) their safety profile has been well delineated in other health conditions in which they are of benefit, (c) they may have complementary mechanisms of action, and (d) the research team has considerable experience with these agents. Target populations will be subjects with a prior history of sporadic adenomatous polyps of the colon within 5 years of entry and no history of previous malignancy. A preliminary Phase 2a trial is designed to determine the minimum dose of aspirin which has relevant biologic activity. A subsequent randomized, double-blind, placebo controlled Phase 2b trial is designed to test the single and combined chemopreventive effects of aspirin and calcium, given for 12 weeks. The aspirin dose will be determined in the phase 2a trial, and the calcium dose will be the previously demonstrated effective dose of 2000 mg/d. The primary endpoints will be colonic mucosal prostaglandin E2 levels and epithelial proliferation indices measured by PCNA methodology. The investigators hypothesize that calcium and aspirin will have a synergistic, risk reducing effect on the colonic mucosa in subjects with a history of adenomatous polyps. The study will be performed in a network of gastroenterologists with access to a large population of adenomatous polyp patients and extensive experience in chemoprevention trials. Data from the phase 2b study will serve to construct a phase 3 study on recurrent polyps.