Pioglitazone in Treating Patients With Newly Diagnosed Stage I or Stage II Non-Small Cell Lung Cancer Who Are Undergoing Surgery

Condition(s) targeted: Lung Cancer

Intervention: pioglitazone hydrochloride (Drug); TdT-mediated dUTP nick end labeling assay (Genetic); immunohistochemistry staining method (Other); laboratory biomarker analysis (Other); therapeutic conventional surgery (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Giuseppe Giaccone, MD, PhD, Principal Investigator, Affiliation: NCI - Medical Oncology Branch

RATIONALE: Pioglitazone may help lung cancer cells become more like normal cells, and grow and spread more slowly.

PURPOSE: This phase II trial is studying how well pioglitazone works in treating patients with newly diagnosed stage I or stage II non-small cell lung cancer who are undergoing surgery.

Official title: Pilot Trial of Pioglitazone in Adults Undergoing Surgical Resection of Non-Small Cell Lung Cancer

Study design: Treatment, Non-Randomized, Open Label

Primary outcome: Effect of pioglitazone hydrochloride on the apoptotic index in tumor tissue as assessed by TUNEL assay

Secondary outcome:

Effect of pioglitazone hydrochloride on tumor tissue biomarkers (i.e., apoptotic index, Ki-67, cyclin D1, p21/Waf1, PPARγ, MUC1, gelsolin, proline oxidase, and 15-hydroxyprostaglandin dehydrogenase)

Effect of pioglitazone hydrochloride on histologically normal bronchial epithelial tissue biomarkers (i.e., Ki-67 and PPARγ)

Effect of pioglitazone hydrochloride on premalignant bronchial epithelial tissue biomarkers (i.e., Ki-67, apoptotic index, and PPARγ)

Effect of pioglitazone hydrochloride on serum biomarkers (i.e., C-reactive protein, CA15-3, CEA, and CA-125)

Clinical response as assessed by FDG-PET in a subset of patients receiving treatment at the National Cancer Institute

Clinical toxicity as assessed by NCI CTCAE v3.0

Detailed description: OBJECTIVES:

Primary

- To evaluate the effect of pioglitazone hydrochloride on the expression of multiple

biomarkers in tumor tissue and in histologically normal and premalignant tissue from patients with newly diagnosed stage I or II non-small cell lung cancer undergoing surgical resection.

Secondary

- To determine the effects of pioglitazone hydrochloride on multiple biomarkers, including

tumor tissue biomarkers (i. e., apoptotic index, Ki-67, cyclin D1, p21/Waf1, PPARγ, MUC1, gelsolin, proline oxidase, and 15-hydroxyprostaglandin dehydrogenase); premalignant bronchial epithelial tissue biomarkers (i. e., Ki-67, apoptotic index, and PPARγ); histologically normal bronchial epithelial tissue biomarkers (i. e., Ki-67 and PPARγ); and serum markers (i. e., C-reactive protein, CA 15-3, CEA, and CA-125).

- To evaluate the toxicity and safety of pioglitazone hydrochloride in these patients.

- To analyze the expression of serum markers that are affected by pioglitazone

hydrochloride.

- To determine whether treatment with pioglitazone hydrochloride affects tumor metabolic

activity as assessed by FDG-PET in a subset of patients treated at the National Cancer Institute.

OUTLINE: This is a multicenter study.

Patients receive oral pioglitazone hydrochloride once daily for 2-6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo definitive surgical resection.

Patients undergo blood and tissue sample collection periodically for biomarker correlative studies. Tissue biomarkers (i. e., apoptotic index, Ki-67, cyclin D1, p21/Waf1, PPARγ, MUC1, gelsolin, proline oxidase, and 15-hydroxyprostaglandin dehydrogenase) are assessed by TUNEL and IHC. Serum markers (i. e., C-reactive protein, CA 15-3, CEA, and CA-125) are also assessed.

Some patients undergo a FDG-PET scan at baseline and after ≥ 2 weeks of treatment with pioglitazone hydrochloride to assess tumor metabolic activity.

Patients are followed at 4-6 weeks after surgery.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed non-small cell lung cancer

- Newly diagnosed disease

- Resectable stage IA-IIB disease

- Scheduled to undergo definitive surgery

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- ANC ≥ 1,500/mL

- Hemoglobin > 10 g/dL

- Platelet count ≥ 100,000/mL

- Bilirubin < 1. 8 mg/dL

- AST and ALT < 1. 5 times upper limit of normal (ULN)

- Creatinine < 1. 5 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective non-hormonal contraception

- Willing to comply with an oral treatment regimen

- Willing to swallow oral study tablets

- Willing to undergo two bronchoscopies during study participation

- No NYHA class II-IV congestive heart failure or history of congestive heart failure

- No edema ≥ grade 2

- No concurrent uncontrolled illness including, but not limited to, any of the

following:

- Ongoing or active infection

- Active liver disease

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would limit compliance with study

requirements

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior radiotherapy to the chest

- More than 1 year since prior radiotherapy to non-chest sites

- More than 1 year since prior chemotherapy or biological therapy

- No concurrent chemotherapy, biological therapy, or radiotherapy

- No concurrent insulin or pharmacologic therapy for treatment of diabetes mellitus

- No concurrent gemfibrozil or rifampin

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office, Bethesda, Maryland 20892-1182, United States; Recruiting
Clinical Trials Office - Warren Grant Magnusen Clinical Center, Phone: 888-NCI-1937

NYU Cancer Institute at New York University Medical Center, New York, New York 10016, United States; Recruiting
Marc Ballas, MD, Phone: 212-731-6645

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2008
Last updated: February 6, 2009