Sulindac in Preventing Lung Cancer in Current or Former Smokers 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|
- 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 ] [ Designated as safety issue: No ]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
- 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 ] [ Designated as safety issue: No ]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.
|Study Start Date:||August 2006|
|Study Completion Date:||December 2010|
|Primary Completion Date:||May 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.
Please refer to this study by its ClinicalTrials.gov identifier: 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|
|Rochester, Minnesota, United States, 55905|
|United States, Ohio|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|Canada, British Columbia|
|Vancouver, British Columbia, Canada, V5Z 1L3|
|Principal Investigator:||James Jett||Mayo Clinic|