Inositol in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia
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.
Non-small Cell Lung Cancer
Squamous Lung Dysplasia
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||Phase IIb Randomized Comparative Study of the Efficacy and Safety of Myo-inositol Versus Placebo in Smokers With Bronchial Dysplasia|
- Change in the histology of bronchial biopsy samples as determined from mucosal biopsy samples [ Time Frame: From baseline up to 6 months ] [ Designated as safety issue: No ]Descriptive statistics will be used to summarize participant characteristics and pathologic evaluations of the bronchial biopsy examinations and compared between groups using Wilcoxon Mann-Whitney test.
- Change in the number of dysplastic lesions before and after treatment [ Time Frame: From baseline up to 6 months ] [ Designated as safety issue: No ]Analyzed within and between the two intervention groups using paired t-tests and two-sample t-tests. Categorized and compared by intervention group using Fisher's exact test or the chi-square test, as appropriate.
- Change in tissue biomarkers (e.g., Ki-67, caspase-3, PPAR gamma, cyclin D1, cyclin E, and VEGF) in bronchial biopsy samples as assessed by IHC, graded on a scale from 0 to II [ Time Frame: From baseline up to 6 months ] [ Designated as safety issue: No ]Analyzed within and between the two intervention groups using paired t-tests and two-sample t-tests.
- Change in gene expression profiles of RNA in bronchial brush cell samples as assessed by microarray [ Time Frame: From baseline up to 6 months ] [ Designated as safety issue: No ]
- Change in inflammatory biomarkers (CRP, MCP-1, MPIF-1, and L-selectin) levels in bronchoalveolar lavage and plasma samples as assessed by ELISA [ Time Frame: From baseline up to 6 months ] [ Designated as safety issue: No ]Fisher's exact tests, Wilcoxon rank sum tests, and two-sample t-tests will be used to assess differences between groups for categorical and continuous outcomes respectively.
- Adverse events, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]The maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number and severity of adverse events (overall and by intervention group) will be tabulated and summarized. Grade 3+ adverse events will be similarly described and summarized separately.
|Study Start Date:||November 2008|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I (inositol)
Patients receive oral inositol once daily for 2 weeks and then twice daily for up to 6 months in the absence of unacceptable toxicity.
Other Name: myo-inositol
Experimental: Arm II (placebo)
Patients receive oral placebo once daily for 2 weeks and then twice daily for up to 6 months in the absence of unacceptable toxicity.
Other Name: PLCB
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.
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.
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New Mexico|
|Albuquerque Veterans Administration Medical Center|
|Albuquerque, New Mexico, United States, 87108-5128|
|Canada, British Columbia|
|BCCA-Vancouver Cancer Centre|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Principal Investigator:||Paul Limburg||Mayo Clinic|