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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00783705
First received: October 31, 2008
Last updated: July 7, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Non-small Cell Lung Cancer
Squamous Lung Dysplasia
Other: placebo
Drug: inositol
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 82
Study Start Date: November 2008
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: inositol
Given orally
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: placebo
Given orally
Other Name: PLCB

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.

  Eligibility

Ages Eligible for Study:   45 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00783705

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Minnesota
Mayo Clinic
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
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Limburg Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00783705     History of Changes
Other Study ID Numbers: NCI-2009-00839, NCI-2009-00839, CDR0000617846, MAY06-8-01, MAY06-8-01, P30CA015083
Study First Received: October 31, 2008
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Inositol
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014