Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Inositol in Preventing Lung Cancer in Current or Former Smokers With Bronchial Dysplasia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Prevention Active 45 to 79 NCI MAYO-MAY06-8-01 MAY06-8-01, NCT00783705

Objectives

Primary

1. To compare the efficacy of inositol vs placebo in reverting bronchial dysplasia in current or former smokers.

Secondary

1. To further define the mechanism(s) of action of pharmacological doses of inositol as a lung cancer chemopreventive agent by evaluating changes in the number of dysplastic lesions and Ki-67, caspase-3, PPAR gamma, cyclin D1, cyclin E, and VEGF immunostaining in bronchial biopsy samples; gene expression of RNA in bronchial brush cell samples; and changes in inflammatory biomarker (e.g., CRP, MCP-1, MPIF-1 and L-selectin) levels in bronchoalveolar lavage and plasma samples obtained before and after treatment.
2. To collect additional safety and adverse event profiles associated with these regimens in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed bronchial dysplasia in ≥ 1 site AND meets one of the following criteria:
  • No history of lung cancer
  • History of stage 0 or I non-small cell lung cancer (NSCLC) curatively treated by surgery (local ablation or resection), adjuvant chemotherapy, or radiotherapy ≥ 6 months ago



• Current or former smoker with ≥ a 30 pack-year smoking history



• 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



• Plasma C-reactive protein level ≥ 1.25 mg/L

Prior/Concurrent Therapy:

• See Disease Characteristics
• 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
• No other concurrent investigational agents

Patient Characteristics:

• 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 CO₂ ≤ 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 ≥ 30 mL/min
• Fasting blood glucose normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to provide a blood sample for C-reactive protein measurement and for cytokine evaluation
• 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)
• SaO₂ ≥ 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

Expected Enrollment

Outcomes

Change in the histology of bronchial biopsy samples before and after treatment

Change in the number of dysplastic lesions before and after treatment
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 before and after treatment
Change in inflammatory biomarker (e.g., CRP, MCP-1, MPIF-1, and L-selectin) levels in bronchoalveolar lavage and plasma samples as assessed by ELISA before and after treatment
Change in gene expression profiles of RNA in bronchial brush cell samples as assessed by microarray before and after treatment
Safety

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 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.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Paul Limburg, MD, MPH, Principal investigator		Ph: 507-284-2511
Stephen Lam, MD, Protocol chair		Ph: 604-675-8089; 800-663-3333

U.S.A.
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623

Registry Information
Official Title		Phase IIb Randomized Comparative Study of the Efficacy and Safety of Myo-inositol versus Placebo in Smokers with Bronchial Dysplasia
Trial Start Date		2008-11-03
Trial Completion Date		2009-10-30 (estimated)
Registered in ClinicalTrials.gov		NCT00783705
Date Submitted to PDQ		2008-10-15
Information Last Verified		2008-12-28