title: Chemoprevention for Barrett's esophagus trial. Design and outcome measures.
abstract: Barrett's esophagus is a premalignant condition in which normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. It is a known risk factor for the development of esophageal adenocarcinoma. With the incidence of esophageal adenocarcinoma rising, it is reasonable to study Barrett's esophagus as a potential target for therapy that may prevent, delay and/or reverse ongoing tumorigenic processes. Epidemiologic and animal studies support the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the chemoprevention of several cancers, including esophageal cancer. Cyclo-oxygenase-2 (COX-2) inhibitors are a new class of NSAIDs that inhibit prostaglandin synthesis by selectively blocking the COX-2 enzyme. The COX-2 enzyme has been reported to be over-expressed in premalignant and malignant states, including in Barrett's esophagus and esophageal adenocarcinoma. The Chemoprevention for Barrett's Esophagus Trial (CBET) is a phase IIb, multicenter, randomized, double-masked, placebo-controlled study of the selective COX-2 inhibitor, celecoxib, in patients with Barrett's dysplasia. The sample size is 200 patients with high or low grade Barrett's dysplasia. Celecoxib is administered orally, 200 mg twice per day; the dosing schedule for placebo is the same. Randomization is stratified by dysplasia grade and by clinic. Endoscopy with biopsies is performed at specified time intervals according to the highest grade of dysplasia determined at randomization. The primary outcome measure is the change from baseline to 1 year in the proportion of biopsies exhibiting dysplasia. Secondary outcomes include change from baseline in the maximal grade, extent and surface area of dysplasia. Tertiary outcomes will include measurements of various relevant biomarkers.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. jshandeih@msn.com
authors.forename: E I
authors.initials: EI
authors.lastname: Heath
authors.forename: M I
authors.initials: MI
authors.lastname: Canto
authors.forename: T-T
authors.initials: TT
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Piantadosi
authors.forename: E
authors.initials: E
authors.lastname: Hawk
authors.forename: A
authors.initials: A
authors.lastname: Unalp
authors.forename: G
authors.initials: G
authors.lastname: Gordon
authors.forename: A A
authors.initials: AA
authors.lastname: Forastiere
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001471:Barrett Esophagus / Q000235:genetics / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D016147:Genes, Tumor Suppressor; D006801:Humans; D008745:Methylation; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors