Sulindac in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia
Condition: Precancerous Condition; Stage I Non-small Cell Lung Cancer; Tobacco Use Disorder
MeSH terms: Lung Neoplasms; Precancerous Conditions; Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): sulindac; placebo
Intervention type(s): Drug; Other
Intervention description(s): Given orally; Given orally
Other intervention name(s): Aflodac; Algocetil; Clinoril; SULIN; PLCB
Intervention MeSH terms: Sulindac
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention