Sulindac in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00368927
Recruitment Status : Completed
First Posted : August 29, 2006
Results First Posted : January 8, 2014
Last Update Posted : May 23, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized phase II trial is studying sulindac to see how well it works compared to a placebo in preventing lung cancer in current or former smokers with bronchial dysplasia. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of sulindac may prevent lung cancer from forming in patients with bronchial dysplasia. It is not yet known whether sulindac is more effective than a placebo in preventing lung cancer in patients with bronchial dysplasia.

Condition or disease Intervention/treatment Phase
Precancerous Condition Stage I Non-small Cell Lung Cancer Tobacco Use Disorder Drug: sulindac Other: placebo Phase 2

Detailed Description:


I. Compare the change in histologic grade of bronchial dysplasia, as determined from mucosal biopsy samples obtained during pre- and post-intervention autofluorescence bronchoscopy exams, in current or former smokers with bronchial dysplasia treated with sulindac vs placebo.


I. Compare the change in number of dysplastic lesions, as determined from mucosal biopsy samples obtained during pre- and post-intervention autofluorescence bronchoscopy exams, in patients treated with these regimens.

II. Compare changes in tissue-based biomarkers (cyclooxygenase [COX]-2, 15-lipoxygenase [LOX]-1, PPAR γ, Ki-67, caspase-3, cyclin D1, cyclin E) in patients treated with these regimens.

III. Determine the safety and adverse event profiles of these regimens in these patients.

IV. Describe the frequency and patterns of bronchial dysplasia as well as biomarker characteristics in patients treated with this regimen.

V. Establish a biospecimen repository archive for future correlative studies.

OUTLINE: This is a multicenter, double-blind, randomized, placebo-controlled study. Patients are stratified according to smoking status (current vs former), prior lung cancer (yes vs no), and number of baseline dysplastic lesions (1-3 vs > 3). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral sulindac twice daily for 6 months.

ARM II: Patients receive oral placebo twice daily for 6 months. Bronchoscopic examination and mucosal biopsy are performed at baseline and at completion of study treatment. Tissue samples are examined by immunohistochemistry for biological markers, including Ki-67, caspase-3, cyclooxygenase-2, cyclin D1, cyclin E, vascular endothelial growth factor, PPAR γ, and 15-lipoxygenase-1. Blood samples are collected for serum cotinine.

After completion of study treatment, patients are followed for up to 30 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Randomized, Phase IIb Trial of Sulindac in Smokers With Bronchial Dysplasia
Study Start Date : August 2006
Actual Primary Completion Date : May 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Sulindac
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Arm I
Patients receive oral sulindac twice daily for 6 months.
Drug: sulindac
Given orally
Other Names:
  • Aflodac
  • Algocetil
  • Clinoril
Placebo Comparator: Arm II
Patients receive oral placebo twice daily for 6 months.
Other: placebo
Given orally
Other Name: PLCB

Primary Outcome Measures :
  1. Percentage of Participants With Response Determined by Change in Histologic Grade of Bronchial Dysplasia as Measured by Mucosal Biopsy Samples Before and After Treatment [ Time Frame: Baseline and 6 months ]
    Definition of response: complete response = regression of all dysplastic lesions (DL) to normal, hyperplasia or metaplasia with no new DL identified; partial response = regression of one or more, but not all of the DL with no new DL identified and no lesions worsening; progression = worsening at one or more sites by at least 2 histologic grades or appearance of any new DL that were not previously biopsied; stable disease = participants not classified as having a complete response, partial response, or progressive disease

Secondary Outcome Measures :
  1. Percent Change in Number of Dysplastic Lesions (DL) as Measured by Mucosal Biopsy Samples Before and After the Intervention [ Time Frame: Baseline and 6 months ]
    The number of dysplastic lesions was recorded pre-intervention and post-intervention for each participant in each group. Change in the number of lesions was compared between the two intervention groups.

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Ages Eligible for Study:   40 Years to 79 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Current or former smoker who has smoked at least 30 pack years AND meets 1 of the following criteria:

    • No prior lung cancer
    • Prior stage I non-small cell lung cancer(NSCLC) that was completely resected ≥ 1 year ago OR for which patient completed adjuvant chemotherapy ≥ 1 year ago
  • Tissue blocks, blood, and sputum samples available for research purposes
  • No carcinoma in situ
  • ECOG performance status 0-1
  • Hemoglobin ≥ 12.0 g/dL (women) or hemoglobin ≥ 13.5 g/dL (men)
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT ≤ 1.5 times ULN
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥30 mL/min
  • Room air oxygen saturation ≥ 90%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Negative chest x-ray
  • Negative electrocardiogram
  • No other cancer within the past 3 years except nonmelanoma skin cancer, localized prostate, carcinoma in situ of the cervix cancer, or superficial bladder cancer

    • Treatment must have been completed > 6 months ago
  • No prior gastrointestinal ulceration, bleeding, or perforation
  • No uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Myocardial infarction within the past 6 months
    • Chronic renal disease
    • Chronic liver disease
    • Difficult to control hypertension
    • Psychiatric illness or social situations that would limit study compliance
  • No known HIV positivity
  • No history of allergic reactions or hypersensitivity to sulindac or other NSAIDs, including aspirin-sensitive asthma or urticaria
  • No known sensitivity to yellow dye FD&C Yellow #5
  • No continuous or intermittent supplemental oxygen
  • At least 6 months since prior participation in another chemoprevention trial
  • At least 6 months since prior regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids (may be eligible after washout period of 12 weeks for NSAIDs and 6 weeks for corticosteroids)
  • No prior pneumonectomy
  • No prior solid organ transplantation
  • No other concurrent investigational agents
  • No concurrent regular use of acetylsalicylic acid (aspirin) unless prescribed by a physician for prevention

    • Maximum of 1 aspirin (81 mg) per day allowed
  • No concurrent use of any of the following:

    • Methotrexate
    • Corticosteroids
    • Antiplatelet agents:

      • Warfarin
      • Ticlopidine
      • Clopidogrel bisulfate
      • Aspirin
      • Abciximab
      • Dipyridamole
      • Eptifibatide
      • Tirofiban hydrochloride
    • Lithium carbonate
    • Cyclosporine
    • Hydralazine
    • Angiotensin-converting enzyme (ACE) inhibitors (ACE receptor antagonists are allowed)
    • Angiotensin receptor blockers

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00368927

United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Massachusetts
Lahey Hospital and Medical Center
Burlington, Massachusetts, United States, 01805
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Canada, British Columbia
British Columbia
Vancouver, British Columbia, Canada, V5Z 1L3
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: James Jett Mayo Clinic

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI) Identifier: NCT00368927     History of Changes
Other Study ID Numbers: NCI-2009-00836
NCI-2009-00836 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MAYO-03-1-02 ( Other Identifier: Mayo Clinic )
MAY03-1-02 ( Other Identifier: DCP )
P30CA015083 ( U.S. NIH Grant/Contract )
N01CN35000 ( U.S. NIH Grant/Contract )
First Posted: August 29, 2006    Key Record Dates
Results First Posted: January 8, 2014
Last Update Posted: May 23, 2014
Last Verified: October 2011

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Tobacco Use Disorder
Precancerous Conditions
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action