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Leukoplakia, OralNCT00299195

A Randomized Study of Sulindac in Oral Premalignant Lesions

A study testing sulindac in people with Leukoplakia, Oral and Benign Neoplasms, run by Memorial Sloan Kettering Cancer Center at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukoplakia, Oral, Benign Neoplasms
What is being tested?
sulindac
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
63 participants
Where
3 sitesin 2 countries
Study dates
23 Feb 2006to 6 Jan 2020
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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
  • is not lactating, AND
  • has a documented negative serum pregnancy test within 14 ds prior to randomization.
  • The subj's history/use of NSAIDs, aspirin, corticosteroids meets the following criteria:
  • total oral/intravenous corticosteroid use has been < 14 ds within 6 mos of the Baseline visit, and
  • total inhaled corticosteroid use has been < 30 ds within 6 mos of the Baseline visit, and
  • is willing to limit aspirin use to < or = 120 mg po per d (typical cardioprotective dose in India) or < or = 80 mg po per d (typical cardioprotective dose in the US) for the duration of the study, and is willing to abstain from chronic use of all NSAIDs and COX-2 inhibitors for duration of study. Chronic use of NSAIDs is defined as a frequency of > or = 3 times/wk AND for more than a total of 14 ds a yr.
  • The subj has discontinued any other chemopreventive therapy at least 3 mos prior to the Baseline visit and all toxicities have been fully resolved.
  • If applicable, the subj has been counseled on smoking cessation.
  • If the subject is male, will use adequate contraception during the study.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

India2 sites

  • Amrita Institute of Sciences (AIMS)

    Kochi

  • Regional Cancer Center (RCC)

    Trivandrum

Other trials in India

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Pilot Multi-Center International Double-Blind Placebo Controlled Randomized Study of Sulindac, a Pan-Cox Inhibitor, 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.

Read the detailed description

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.

Being tested
sulindac, Placebo
Keywords
Oral Leukoplakia, Benign Neoplasms, Chemoprevention, Pan-cyclooxygenase (COX) inhibitor, sulindac, 04-099
Medical subject headings
Leukoplakia, Oral, Neoplasms, Coproporphyria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • sulindacDrug

    Sulindac 150 mg po bid x 24 weeks

  • PlaceboDrug

    Placebo bid x 24 weeks

Study groups in NCT00299195
Study groupRoleWhat they receive
1Experimentalsulindac
Receives: Drug: sulindac
2Placebo comparatorplacebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: after 24 weeks of study drug

Secondary outcomes (4)

  1. 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.

    Measured: after 24 weeks of study drug

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

    Measured: baseline and after 24 weeks

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

    Measured: week 4, 8, 12, 16, 20 and 24

  4. To Explore the Relationship Between Genetic Polymorphisms of Genes Involved in Carcinogenesis and Clinical or Biomarker Response to Sulindac

    Measured: after 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2006 (estimated)
  2. Study start23 Feb 2006
  3. Primary completion6 Jan 2020
  4. Study completion6 Jan 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
63 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00299195
Sponsor's protocol ID
04-099
Status last verified
Jan 2020
First submitted
2 Mar 2006
Last updated
19 Nov 2020

Questions about this trial

What is this clinical trial studying?

A study testing sulindac in people with Leukoplakia, Oral and Benign Neoplasms, run by Memorial Sloan Kettering Cancer Center at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in India, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

- 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00299195.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2020.

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