A Randomized Study of Sulindac in Oral Premalignant Lesions
The purpose of this study is to see if a drug called sulindac can prevent the development of changes in the mouth that are related to oral pre-cancer growths (oral epithelial dysplasia) or oral cancer. Sulindac is an anti-inflammatory drug that has already been tested in people with arthritis (inflammation of a joint).
This study is being done by Memorial Sloan-Kettering Cancer Center in New York, Amrita Institute of Medical Sciences and Research Center in Cochin, India, and Regional Cancer Centre (RCC) in Trivandrum, India.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Pilot Multi-Center International Double-Blind Placebo Controlled Randomized Study of Sulindac, a Pan-Cox Inhibitor, in Oral Premalignant Lesions|
- - 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). [ Time Frame: after 24 weeks of study drug ] [ Designated as safety issue: No ]
- To evaluate the effect of sulindac in modulating the expression of the intermediate biomarkers Ki67, p53 proteins and DNA ploidy after 24 weeks of treatment of study drug, and again after 8 weeks off study drug. [ Time Frame: after 24 weeks of study drug ] [ Designated as safety issue: No ]
- To evaluate the correlation between baseline COX-2 expression or DNA ploidy with clinical response or biomarker modulation [ Time Frame: baseline and after 24 weeks ] [ Designated as safety issue: No ]
- To evaluate the safety of chronic dosing of sulindac in this subject population [ Time Frame: week 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: Yes ]
- To explore the relationship between genetic polymorphisms of genes involved in carcinogenesis and clinical or biomarker response to sulindac [ Time Frame: after 24 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||February 2006|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Sulindac 150 mg po bid x 24 weeks
Placebo Comparator: 2
Placebo bid x 24 weeks
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 in India.
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.
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Amrita Institute of Sciences (AIMS)|
|Regional Cancer Center (RCC)|
|Principal Investigator:||Jay O. Boyle, M.D.||Memorial Sloan-Kettering Cancer Center|