Chemoprevention with enzastaurin: First-year results

Abstract

1520 Background: Chemoprevention is crucial for reducing lung cancer mortality. The implementation and conduct of such trials is complex. We evaluated accrual in an ongoing trial. Methods: We are conducting a study evaluating if enzastaurin, a protein kinase C beta inhibitor, decreases the Ki-67 labeling index in bronchial epithelium after 6 months of therapy compared to placebo. Eligibility includes age 45 or younger, smoking 30 or fewer packs per year, quit for less than one 1 year, and bronchial meta/dysplasia. Results: Two-thousand eight hundred and nine potential subjects were selected from our database. Between December 2007 and November 2009, 1,242 were invited to participate by an introductory letter and at least 3 attempted telephone contacts. Phone contact was established with 621 (50%) subjects. 245 (39%) declined, 238 (38%) were ineligible, and 138 (22%) were interested in trial participation. At the first face-to-face visit, 57 out of 138 (38%) were eligible, 71 (51%) had not quit smoking for less than 1 year, one (1%) was ineligible for other reasons, and nine (7%) visits are pending. All 57 eligible subjects had an induced sputum exam: 36 had atypia, 19 were normal, and two were inadequate. Bronchoscopies with white light and laser-induced fluorescence and three or fewer biopsies have been done on 22 subjects (4 pending, 4 withdrew, 6 ineligible for bronch). Three had normal histology at all sites, 16 had metaplasia, and two had dysplasia in at least one site (84% abnormal bronchial histology rate, 1 pending). No occult cancers were identified. Conclusions: Of 1,242 preselected potential participants, 11% presented for a first face-to-face visit, 4.6% were eligible after a sputum exam, and 2.4% were fully eligible for randomization. Thus, to reach the accrual goal of 186 patients, we estimate that we will need to contact 7,700 subjects. During our 12-month period, we accessed 1,242 patients with 2.0 FTE for study coordinators (not including the pathologist, bronchoscopist, and laboratory personnel). Our expectation had been to accomplish accrual over a period of 42 months from a pool of 2,809 existing putative patients. Unless our eligibility rate of 2.4% increases, further sources of patients must be identified to accomplish our accrual goal. No significant financial relationships to disclose.