A Randomized Study of Sulindac in Oral Premalignant Lesions

NCT00299195 | Completed Results

• 1 other identifier: 04-099
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 3

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.

Conditions

Leukoplakia, Oral; Benign Neoplasms

Keywords

Oral Leukoplakia; Benign Neoplasms; Chemoprevention; Pan-cyclooxygenase (COX) inhibitor; sulindac; 04-099

Outcome Measures

Primary Outcomes (1)

• - 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

Secondary Outcomes (4)

• 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.

  after 24 weeks of study drug

• To Evaluate the Correlation Between Baseline COX-2 Expression or DNA Ploidy With Clinical Response or Biomarker Modulation

  baseline and after 24 weeks

• To Evaluate the Safety of Chronic Dosing of Sulindac in This Subject Population

  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

  after 24 weeks

Study Arms (2)

1

EXPERIMENTAL

sulindac

Drug: sulindac

2

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

sulindac DRUG

Sulindac 150 mg po bid x 24 weeks

1

Placebo DRUG

Placebo bid x 24 weeks

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For this study an Oral Premalignant Lesions (OPL) is defined as a lesion which can include atypical hyperplasia, atypical hyperkeratosis, leukoplakia, and erythroplakia/erythro-leukoplakia. Histology MUST be confirmed by an MSKCC pathologist for all participating sites. An OPL may be located in the oral cavity, oropharynx.
• The subj has a histologically suspected or confirmed index oral premalignant lesion, 12mm or greater in size that has not been bx'd in the past 6 wks. Each index lesion must be either:
• An EARLY premalignant lesion defined to be at high risk as indicated by the presence of at least one of the following: atypical cells or mild dysplasia, or hyperplastic leukoplakia of high-risk sites, lateral and ventral tongue and floor or mouth OR
• An ADVANCED premalignant lesion defined as the presence of at least one of the following: moderate dysplasia or severe dysplasia (excluding CIS)
• The subj is \> 18 yrs of age
• The subj's life expectancy is \> 12 wks and Zubrod performance status is 0 or 1 (Appendix VIII).
• The subj meets the following lab eligibility criteria during a time not to exceed 4 wks prior to randomization.
• Hemoglobin level above 10g/dL for women and above 12g/dL for men.
• WBC count \> 3,000 uL.
• Platelets count \> 125,000 uL.
• Total bilirubin \< or = 1.5xULN
• AST (SGOT) and ALT (SGPT) \< or = 2.5 x ULN.
• BUN and serum creatinine \< or = 1.5 x ULN.
• If the subj is female and of childbearing potential (women are considered not of childbearing potential if they are at least 2 yrs postmenopausal and/or surgically sterile), she:
• has been using adequate contraception (abstinence, IUD, birth control pills, or spermicidal gel with diaphragm or condom) since her last menses and will use adequate contraception during the study, AND

You may not qualify if:

• The subject has had chemotherapy, immunotherapy, hormonal tx (other than HRT for menopause), or RT within 3 wks of the Baseline visit.
• The subj has not recovered from the acute toxic effects of chemotherapy, immunotherapy, hormonal tx, or RT.
• The subj will need concurrent chemotherapy, radiotherapy, hormonal (other than HRT for menopause), or immunotherapy during the time of study.
• The subj has a history of hypersensitivity to sulindac, COX-2 inhibitors, NSAIDs, salicylates.
• The subj has been diagnosed with or has been treated for esophageal, gastric, pyloric channel, or duodenal ulceration.
• The subj has a history of inv cancer within the past 1 yr (excluding non-melanoma skin cancer and in situ cervical cancer).
• The subj has a chronic or acute renal or hepatic disorder or a significant bleeding disorder or any other condition which, in the Institutional Principal Investigator's opinion, might preclude study participation.
• The subj has a past history of or active inflammatory bowel disease (eg. Crohn's disease or ulcerative colitis) or pancreatic disease.
• The subj has received any investigational medication within 30 ds of the Baseline visit or is scheduled to receive an investigational drug during the course of the study.
• The subj is, in the opinion of the Institutional Principal Investigator, not an appropriate candidate for study participation.
• The subj participated in the study previously and was withdrawn.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AIMS Institute: collaborator
• Weill Medical College of Cornell University: collaborator
• Regional Cancer Centre, Trivandrum, India: collaborator
• Narayana Hrudayalaya Hospitals: collaborator

Study Sites (3)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Amrita Institute of Sciences (AIMS)

Kochi, India

Location

Regional Cancer Center (RCC)

Trivandrum, India

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukoplakia, Oral; Neoplasms; Coproporphyria

Interventions

Sulindac

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Leukoplakia; Precancerous Conditions; Mouth Diseases; Stomatognathic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Jay Boyle, MD
• Organization: Memorial Sloan Kettering Cancer Center

boylej@mskcc.org

212-639-2906

Study Officials

• Jay O. Boyle, M.D.

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2006
• First Posted: March 6, 2006
• Study Start: February 23, 2006
• Primary Completion: January 6, 2020
• Study Completion: January 6, 2020
• Last Updated: November 19, 2020
• Results First Posted: November 19, 2020

Record last verified: 2020-01

Locations

IN (2); US (1)