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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Response determined by change in histologic grade of bronchial dysplasia as measured by mucosal biopsy samples before and after treatment
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.
Baseline and 30 days
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|