? The proposed trial is a phase II randomized, double-blind, placebo-controlled chemoprevention pilot trial of 150 mg bid sulindac for 6 months for oral premalignant lesions (OPL). The objective is to determine the feasibility of conducting such studies 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. This State has one of the highest incidences of oral cancer and leukoplakia in the world due to habits of tobacco exposure. The study seeks also to determine the clinical efficacy and safety of sulindac against OPL and to determine the effect of sulindac on biomarkers in OPL tissue. The biomarkers are DNA ploidy, Ki67 IHC, p53 IHC, and baseline COX-2 expression. 66 subjects will be enrolled from the Amrita Institute for Medical Sciences over a 6-12 month period. All data management and biomarkers will be performed At MSKCC in New York except DNA ploidy, which will be measured at AIMS. ? ? After initial biopsy, subjects will be stratified for the presence of either early premalignant lesions (atypical hyperplasia, atypical hyperkeratosis, mild dysplasia) or advanced premalignant lesions (moderate or severe dysplasia or CIS). This will ensure equal distribution of high grade lesions into placebo and sulindac arms. Subjects will then be randomized to either sulindac 150 mg bid or placebo bid for six months. At the end of six months of treatment the lesion will be measured for the primary assessment of clinical efficacy, and biopsied for assessment of secondary endpoint biomarkers. Subjects will remain under observation for two additional months at which time the lesions will be measured and assessed for clinical change and biopsied for biomarker assessment. These final assessments can be compared to those at baseline and at 6 months to assess the durability of treatment effects. The study is powered to achieve an 80% chance of identifying a 30% response rate. The study is planned to accrue for 12 months and to be completed in 24 months. Not only will this study prove the feasibility of performing such trials but will also provide preliminary data for efficacy of COX inhibitors for tobacco related cancers, and for comparing biology of these lesions in India to those previously studied in the West. This high risk population will benefit from these advances. ? ?
