Sulindac in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia
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.
Stage I Non-small Cell Lung Cancer
Tobacco Use Disorder
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||Randomized, Phase IIb Trial of Sulindac in Smokers With Bronchial Dysplasia|
- Response determined by change in histologic grade of bronchial dysplasia as measured by mucosal biopsy samples before and after treatment [ Time Frame: Baseline and 30 days ] [ Designated as safety issue: No ]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.
- Change in number of dysplastic lesions as measured by mucosal biopsy samples before and after treatment [ Time Frame: Pre-intervention and post-intervention ] [ Designated as safety issue: No ]Will be analyzed within and between the two intervention groups using paired t-tests and two-sample t-tests. Univariate and multivariate regression models will be fit using percent change in the number of bronchial dysplastic lesions as the response variable and intervention group, smoking status, demographic features and other clinical characteristics as predictor variables, as appropriate. Pending distribution of the data, change in the number of dysplastic lesions within each participant will be categorized and compared by intervention group using Fisher's exact test or the chi-square test.
|Study Start Date:||August 2006|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral sulindac twice daily for 6 months.
Placebo Comparator: Arm II
Patients receive oral placebo twice daily for 6 months.
Other Name: PLCB
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.
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||James Jett||Mayo Clinic|