Inositol in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia
Condition: Non-small Cell Lung Cancer; Squamous Lung Dysplasia
MeSH terms: Lung Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This randomized phase II trial is studying inositol to see how well it works compared with 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. The use of inositol
      may prevent lung cancer. It is not yet known whether inositol is more effective than a
      placebo in preventing lung cancer in smokers with bronchial dysplasia.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To evaluate the efficacy of myo-inositol (inositol) 9 grams by mouth twice a day for 6
      months versus placebo to revert bronchial dysplasia in current/former smokers with or without
      curatively treated Stage 0/I non-small cell lung cancer.

      SECONDARY OBJECTIVES:

      I. To further define the mechanism(s) of action of pharmacological doses of myo-inositol as a
      lung cancer chemopreventive agent by evaluating changes in: the number of dysplastic lesions,
      Ki-67, caspase-3, peroxisome proliferator-activated receptor (PPAR) gamma, cyclin D1, cyclin
      E and vascular endothelial growth factor (VEGF) immunostaining in bronchial biopsies; gene
      expression analysis of ribonucleic acid (RNA) from bronchial brush cells; and changes in
      inflammatory biomarkers (C-reactive protein [CRP], monocyte chemotactic protein-1 [MCP-1],
      myeloid progenitor inhibitory factor-1 [MPIF-1] and L-Selectin) levels in bronchoalveolar
      lavage (BAL) and plasma before and after treatment.

      II. To collect additional safety and adverse event profiles of participants enrolled in both
      intervention arms. III. To establish a biospecimen repository archive for future correlative
      studies.

      OUTLINE: Patients are stratified according to smoking status (current vs former), prior lung
      cancer (yes vs no), and number of dysplastic lesions at baseline (1 vs > 1). Patients are
      randomized to 1 of 2 treatment arms.

      ARM I: Patients receive oral inositol once daily for 2 weeks and then twice daily for up to 6
      months in the absence of unacceptable toxicity.

      ARM II: Patients receive oral placebo once daily for 2 weeks and then twice daily for up to 6
      months in the absence of unacceptable toxicity.

      Patients undergo white light and autofluorescence bronchoscopy with bronchoalveolar lavage,
      bronchial brushings, and biopsies as well as optical coherence tomography imaging and blood
      sample collection at baseline and after completion of study treatment. Samples are analyzed
      for tissue biomarkers (e.g., PPAR gamma, Ki-67, caspase-3, cyclin D1, cyclin E, and VEGF) by
      immunohistochemistry (IHC); cytokine levels (e.g., CRP, MCP-1, MPIF-1, and L-selectin) by
      ELISA; and gene expression profiles of RNA by microarray.

      After completion of study treatment, patients are followed within 30 days.
    

Intervention name(s): placebo; inositol
Intervention type(s): Other; Drug
Intervention description(s): Given orally; Given orally
Other intervention name(s): PLCB; myo-inositol
Intervention MeSH terms: Inositol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention