Clinical Trial: A Randomized Study of Sulindac in Oral Premalignant Lesions

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Pilot Multi-Center International Double-Blind Placebo Controlled Randomized Study of Sulindac, a Pan-Cox Inhibitor, in Oral Premalignant Lesions

Brief Summary:

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.


Detailed Summary:

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 t
Sponsor: Memorial Sloan Kettering Cancer Center

Current Primary Outcome: - 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 ]

Original Primary Outcome: - 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).

Current Secondary Outcome:

  • 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 ]
  • 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 ]
  • To evaluate the safety of chronic dosing of sulindac in this subject population [ Time Frame: week 4, 8, 12, 16, 20 and 24 ]
  • To explore the relationship between genetic polymorphisms of genes involved in carcinogenesis and clinical or biomarker response to sulindac [ Time Frame: after 24 weeks ]


Original Secondary Outcome:

  • - 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.
  • - To evaluate the correlation between baseline COX-2 expression or DNA ploidy with clinical response or biomarker modulation
  • - To evaluate the safety of chronic dosing of sulindac in this subject population
  • - To explore the relationship between genetic polymorphisms of genes involved in carcinogenesis and clinical or biomarker response to sulindac


Information By: Memorial Sloan Kettering Cancer Center

Dates:
Date Received: March 2, 2006
Date Started: February 2006
Date Completion: June 2017
Last Updated: June 6, 2016
Last Verified: June 2016