Phase IIb Randomized Comparative Study of the Efficacy and Safety of Myo-inositol Versus Placebo in Smokers With Bronchial Dysplasia
45 Years
79 Years
Both
Non-small Cell Lung Cancer, Squamous Lung Dysplasia
Trial Information
Phase IIb Randomized Comparative Study of the Efficacy and Safety of Myo-inositol Versus Placebo in Smokers With Bronchial Dysplasia
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.
Inclusion Criteria:
- Histologically confirmed bronchial dysplasia in ≥ 1 site AND meets one of the
following criteria:
- Current or former smoker with ≥ a 30 pack-year smoking history and no history of
lung cancer
- Stage 0 or I non-small cell lung cancer (NSCLC) curatively treated by surgery
(local ablation or resection), adjuvant chemotherapy, or radiotherapy with a ≥
30 pack-year smoking history
- At least 6 months since prior surgery, adjuvant chemotherapy, or
radiotherapy
- No current evidence of lung cancer by CT scan
- No non-calcified lung nodules ≥ 10 mm diameter on spiral CT scan unless cancer
is ruled out by PET/CT scan or by biopsy
- ECOG performance status 0-1
- Hemoglobin normal
- Leukocyte count ≥ 3,000/mm³
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 1.5 times ULN
- ALT and AST ≤ 1.5 times ULN
- BUN ≤ 1.5 times ULN
- Chloride ≤ 1.5 times ULN
- Total CO_2 ≤ 1.5 times ULN
- Sodium ≤ 1.5 times ULN
- Calcium ≤ 1.5 times ULN
- Potassium ≤ 1.5 times ULN
- Phosphorus ≤ 1.5 times ULN
- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 30mL/min
- Fasting blood glucose normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No cancer within the past 3 years except stage 0 or I NSCLC, nonmelanomatous skin
cancer, localized prostate cancer, carcinoma in situ of the cervix, or superficial
bladder cancer that was treated > 6 months ago
- No concurrent uncontrolled illness including, but not limited to, any of the
following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Severe chronic obstructive pulmonary disease requiring supplemental oxygen
- Uncontrolled hypertension
- Psychiatric illness or social situation that would limit compliance with study
requirements
- No schizophrenia or bipolar disorder
- No diabetes
- No requirement for supplemental oxygen (continuous or intermittent)
- SaO_2 ≥ 90% on room air
- No history of allergic reactions attributed to inositol
- No history of allergies to any ingredient in the study agent or placebo
- No other concurrent investigational agents
- At least 7 days since prior anticoagulant use (e.g., coumadin or heparin)
- More than 6 months since prior participation in another chemoprevention clinical
trial
- No prior pneumonectomy
- No prior solid organ transplantation
- No concurrent lithium, carbamazepine, or valproate
- No concurrent use of other natural health products containing inositol
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Outcome Measure:
Change in the histology of bronchial biopsy samples as determined from mucosal biopsy samples
Outcome Description:
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.
Outcome Time Frame:
From baseline up to 6 months
Safety Issue:
No
Principal Investigator
Paul Limburg
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00839
NCT ID:
NCT00783705
Start Date:
November 2008
Completion Date:
Related Keywords:
- Non-Small Cell Lung Cancer
- Squamous Lung Dysplasia
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
- Hyperplasia
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
| Mayo Clinic in Arizona | Scottsdale, Arizona 85259-5404 |
| Albuquerque Veterans Administration Medical Center | Albuquerque, New Mexico 87108-5128 |
