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Randomized, Phase IIb Trial of Sulindac in Smokers With Bronchial Dysplasia

Phase 2
40 Years
79 Years
Not Enrolling
Precancerous Condition, Stage I Non-small Cell Lung Cancer, Tobacco Use Disorder

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Trial Information

Randomized, Phase IIb Trial of Sulindac in Smokers With Bronchial Dysplasia


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


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

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.

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

- Angiotensin receptor blockers

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Outcome Measure:

Response determined by change in histologic grade of bronchial dysplasia as measured by mucosal biopsy samples before and after treatment

Outcome Description:

Will be explored graphically within and across the two intervention arms. The two-sample Smirnov test (a non-linear rank test based on hypergeometric distribution) will be used to perform a more thorough analysis of ordered categories. Odds ratios along with 95% confidence intervals will be estimated.

Outcome Time Frame:

Baseline and 30 days

Safety Issue:


Principal Investigator

James Jett

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

August 2006

Completion Date:

Related Keywords:

  • Precancerous Condition
  • Stage I Non-small Cell Lung Cancer
  • Tobacco Use Disorder
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Precancerous Conditions
  • Tobacco Use Disorder



Mayo ClinicRochester, Minnesota  55905
H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612