Funding is requested to plan a multi-center, randomized, double-blind, placebo-controlled chemoprevention trial of sulindac for oral leukoplakia through an international collaboration between Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and the Amrita Institute of Medical Sciences (AIMS) in Kerala, India. An informal, yet critical objective of the proposed trial is to determine the feasibility of conducting such international studies in populations in which the prevalence of oral cancer and ieukoplakia are among the highest in the world. The primary scientific objective is to test the clinical efficacy and safety of sulindac against oral premalignant lesions (OPL) and biomarkers in OPL tissue (DNA ploidy, Ki67 and p53 IHC, COX-2 expression). 66 oral leukoplakia patients will be enrolled from both AIMS and MSKCC. Patients will be randomized to receive either sulindac 150-mg bid or placebo [unreadable]bid for 6 months, and will remain under observation for an additional two months. All data management and biomarkers will be performed at MSKCC except DNA ploidy, which will be measured at AIMS. The objective of this planning grant is to develop a complete manual of procedures (MOP) to facilitate consistency in protocol implementation and data collection across patients and between clinic sites. The specific aims of the planning grant are to: 1) refine the study protocol and data and safety monitoring plan, 2) prepare the agent for clinical trial use (bioavailability, packaging, shipping, regulatory) 3) establish procedures for packing, labeling and shipping drug and biological specimens, 4) further refine the plan for biomarkers including DNA ploidy, and genetic polymorphisms. The proper planning of each aspect of this international trial is time consuming and yet critical to the safe and successful completion. Performing these trials in endemic regions is necessary to advance the field.
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