Conditions: Precancerous Condition Stage I Non-small Cell Lung Cancer Tobacco Use Disorder
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 61
Healthy volunteers: no

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.

Detailed description:
PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

Arms:
arm 1: Patients receive oral sulindac twice daily for 6 months. arm 2: Patients receive oral placebo twice daily for 6 months.

Interventions: intervention 1: sulindac intervention 2: placebo
Intervention descriptions: intervention 1: Given orally intervention 2: Given orally

Protocol document: