Pioglitazone for Lung Cancer Chemoprevention

Lung Cancer Clinical Trial

Official title:

Pioglitazone for Lung Cancer Chemoprevention

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00780234
• Other study ID #: CLIN-005-08S
• Status: Completed
• Phase: Phase 2
• Start date: August 2009
• Est. completion date: August 2017

Study information

• Verified date: April 2019
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: August 2017
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endobronchial Dysplasia
• Lung Cancer
• Lung Neoplasms

Intervention

Procedure:
• fluorescence bronchoscopy
examination of the central airways with a bronchoscope. Both white light and fluorescent light will be used.
• 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.

Locations

Country	Name	City	State
United States	VA Eastern Colorado Health Care System, Denver, CO	Denver	Colorado
United States	Tennessee Valley Healthcare System Nashville Campus, Nashville, TN	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   Oral iloprost improves endobronchial dysplasia in former smokers