CHEMOPREVENTION OF DEFLUOROMETHYLORNITHINE IN INTESTINAL BARRETTS ESOPHAGUS

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We propose a Phase IIb clinical trial of alpha-difluoromethylornithine (DFMO), a potent inhibitor of ornithine decarboxylase, a crucial enzyme in the spermine synthesis pathway which is required for cellular growth as a potential treatment to prevent the progression of Barrett's esophagus to invasive adenocarcinoma. This Phase IIb study is designed to determine whether DFMO, given in a double-blinded, placebo-controlled clinical trial will alter cellular proliferation in human subjects with dysplastic or metaplastic Barrett's esophagus. Human subjects with intestinal type Barrett's metaplasia or mild dysplasia will be treated with DFMO, 900 mg daily, or placebo in a randomized, double blinded design for 6 months. Prior, 6 months, and 13 months after treatment, endoscopy with biopsies of the Barrett's esophagus, normal esophagus, and normal gastric mucosa will be obtained and studied for surrogate endpoint biomarkers (proliferation, apoptosis, cellular morphometry, microsatellites, p53, and transforming growth factors).