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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Non-small Cell Lung Cancer

Squamous Lung Dysplasia

Treatments

Other: placebo

Drug: inositol

Study type

Interventional

Funder types

NIH

Identifiers

NCT00783705

P30CA015083 (U.S. NIH Grant/Contract)

CDR0000617846

NCI-2009-00839 (Registry Identifier)

MAY06-8-01 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

85 patients

Sex

All

Ages

45 to 79 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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