Pioglitazone for Lung Cancer Chemoprevention

Study Overview
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Brief Summary
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This is a chemoprevention trial evaluating the diabetic agent pioglitazone. Non-diabetic subjects at risk for lung cancer (based on smoking history, lung function testing, and atypical cells in a sputum sample) receive either placebo or pioglitazone and have chest computerized tomography (CAT) scans and examinations of their airways with a bronchoscope at the start of the trial and after 6 months on treatment. Compensation will be provided to the subject after completing the trial.

Detailed Description
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This trial evaluates the oral peroxisome proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone in a double-blind placebo controlled trial. The high risk current and former smokers qualify based on tobacco exposure, airflow limitation on lung function testing, and sputum cytologic atypia. Subjects have a quantitative high resolution thoracic CT scan and a fluorescent bronchoscopy at study entry and after 6 months on drug or placebo. Biologic samples are collected at both time points. The primary outcome is endobronchial histology and determining if pioglitazone can retard progression. Secondary endpoints related to the PPAR gamma signaling pathway will also be analyzed.

Official Title
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Pioglitazone for Lung Cancer Chemoprevention

Conditions
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Lung Cancer, Endobronchial Dysplasia

Intervention / Treatment
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* Procedure: fluorescence bronchoscopy
* Procedure: quantitative high resolution CT scan
* Drug: PIOGLITAZONE VS. PLACEBO 30 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current or former smoker (at least 10 pack years); One or more of the following: Mild or worse sputum atypia Airflow Limitation (FEV1/FVC<70% predicted) Biopsy proven airway dysplasia Exclusion Criteria: myocardial infarction (MI) with ejection fraction < 50%; severe/unstable angina; history of coronary or peripheral arterial bypass grafting; New York Heart Association (NYHA) class III or IV congestive heart failure; hypoxemia (less than POX 90 with supplemental oxygen); Diabetes type I or II; severe COPD (GOLD stage III or IV); clinically significant edema requiring diuretic therapy; life expectancy < 6 months; history of bladder cancer pregnant or breast feeding; inability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: pioglitazone<br>Current or former smokers receive 6 months of treatment with pioglitazone | Procedure: fluorescence bronchoscopy<br>* examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.<br>Procedure: quantitative high resolution CT scan<br>* High resolution CT scan of the chest<br>Drug: PIOGLITAZONE VS. PLACEBO 30 mg<br>* Patients will be randomized to receive either pioglitazone or placebo. Pioglitazone hydrochloride, a thiazolidinedione antidiabetic agent and a potent peroxisome proliferator- activated receptor-gamma agonist. It is FDA approved for the treatment of Type II diabetes. It has been previously administered to non-diabetic subjects. The most common side effect of pioglitazone is fluid retention and modest weight gain. There is a potential risk that pioglitazone may cause an elevation in liver enzymes and more serious hepatotoxicity (rare). There is risk of edema and weight gain associated with pioglitazone therapy. 5% experienced peripheral edema in clinical trials. fluid retention may result in new onset heart failure or exacerbation of existing heart failure. Small risk of hypoglycemia, anemia, myalgia, bone fracture, headache, and macular retinal edema exists. There is insufficient information to confirm its safety in Pregnancy/Breastfeeding. Bladder cancer is more serious but rare.<br>|
| Placebo Comparator: Arm 2: placebo<br>Current or former smokers receive 6 months of treatment with placebo | Procedure: fluorescence bronchoscopy<br>* examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.<br>Procedure: quantitative high resolution CT scan<br>* High resolution CT scan of the chest<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month Histology Score | Biopsies were classified into one of the following 8 World Health Organization defined categories to classify the endobronchial lesion and assign a score according to the following scale: 1 = normal bronchial epithelium; 2 = reserve cell hyperplasia; 3 = squamous metaplasia without atypia; 4 = mild dysplasia; 5 = moderate dysplasia; 6 = severe dysplasia; 7 = carcinoma in situ (CIS); and 8 = invasive carcinoma. 1 represents the best outcome and 8 represents the worst outcome. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemoprevention, lung cancer, pioglitazone