Pioglitazone for Lung Cancer Chemoprevention

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer; Endobronchial Dysplasia	Procedure: fluorescence bronchoscopy; Procedure: quantitative high resolution CT scan; Drug: PIOGLITAZONE VS. PLACEBO 30 mg	Phase 2

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	391 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	Pioglitazone for Lung Cancer Chemoprevention
Study Start Date :	August 2009
Actual Primary Completion Date :	June 2016
Estimated Study Completion Date :	August 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Arm 1: pioglitazone; Current or former smokers receive 6 months of treatment with pioglitazone	Procedure: fluorescence bronchoscopy; examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used. Procedure: quantitative high resolution CT scan; High resolution CT scan of the chest Drug: PIOGLITAZONE VS. PLACEBO 30 mg; 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.
Placebo Comparator: Arm 2: placebo; Current or former smokers receive 6 months of treatment with placebo	Procedure: fluorescence bronchoscopy; examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used. Procedure: quantitative high resolution CT scan; High resolution CT scan of the chest

Outcome Measures

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Primary Outcome Measures :

1. Changes in endobronchial histology [ Time Frame: 6 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

United States, Colorado
VA Eastern Colorado Health Care System, Denver, CO
Denver, Colorado, United States, 80220
United States, Tennessee
Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
Nashville, Tennessee, United States, 37212-2637

Sponsors and Collaborators

VA Office of Research and Development

Investigators

Principal Investigator:	Robert L. Keith, MD	VA Eastern Colorado Health Care System, Denver, CO

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Oral iloprost improves endobronchial dysplasia in former smokers 

Responsible Party:	VA Office of Research and Development
ClinicalTrials.gov Identifier:	NCT00780234 History of Changes
Other Study ID Numbers:	CLIN-005-08S
First Posted:	October 27, 2008
Last Update Posted:	October 3, 2016
Last Verified:	September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by VA Office of Research and Development:

chemoprevention; lung cancer; pioglitazone

Additional relevant MeSH terms:

Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms	Lung Diseases; Respiratory Tract Diseases; Pioglitazone; Hypoglycemic Agents; Physiological Effects of Drugs