A Pilot Multi-Center International Double-Blind Placebo Controlled Randomized Study of Sulindac, a Pan-Cox Inhibitor, in Oral Premalignant Lesions
Oral precancerous lesions (OPL) represent a valuable model for clinical trials for tobacco
related cancers. However, due to the relatively low prevalence of this condition in the
United States, subject accrual to such trials is slow. Conversely, in India, the prevalence
of oral leukoplakia is among the highest in the world. Indeed oral cancer, caused by
exposure to tobacco smoke, alcohol and betel nut quid, is the leading cause of cancer deaths
To date, there are no effective treatments documented in randomized controlled clinical
trials to prevent malignant transformation of leukoplakia. However, evidence that
non-steroidal anti-inflammatory drugs (NSAIDs) prevent experimental and animal head and neck
cancer, and colon and breast cancer in humans lends support to the promise of NSAIDs in the
chemoprevention of oral cancer.
The purpose of this protocol is to pilot a multi-center chemoprevention trial of sulindac, a
pan-cyclooxygenase (COX) inhibitor, for oral leukoplakia through an international
collaboration between Memorial Sloan-Kettering Cancer Center (MSKCC), New York, Regional
Cancer Centre (RCC) in Trivandrum, India and the Amrita Institute of Medical Sciences
(AIMS), Kerala, India. Specifically, we will conduct a 66 subject, 2-arm, double-blind,
placebo-controlled randomized study of sulindac 150 mg bid to test the clinical efficacy,
safety and molecular effects of sulindac against OPL and OPL tissue. Oral leukoplakia
subjects will be enrolled from both RCC, AIMS and MSKCC, however, we expect that most
subjects will be recruited from AIMS due to the substantially higher prevalence of this
condition among the Indian compared to the US population.
MSKCC will be the coordinating center for this trial, and will thus be responsible for all
aspects of clinical trial design and management. Our study team, in collaboration with the
Office of Clinical Research and the Office of the Physician-in-Chief, has spent a
considerable amount of time and effort in developing a comprehensive data and safety
monitoring (DSM) plan.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
- To evaluate the efficacy of sulindac in subjects with early or advanced oral premalignant lesion (OPL) by both clinical response (reduction in size of all lesions) and histological response (change in histological grade).
after 24 weeks of study drug
Jay O. Boyle, M.D.
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|