Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Active 18 and over NCI NCI-08-C-0208 08-C-0208, NCT00751725

Special Category: NIH Clinical Center trial

Objectives

Primary

1. 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

1. 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).
2. To evaluate the toxicity and safety of pioglitazone hydrochloride in these patients.
3. To analyze the expression of serum markers that are affected by pioglitazone hydrochloride.
4. 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.

Entry Criteria

Disease Characteristics:

• Histologically confirmed non-small cell lung cancer
  • Newly diagnosed disease
  • Resectable stage IA-IIB disease



• Scheduled to undergo definitive surgery

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

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

Expected Enrollment

Outcomes

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

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

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

Giuseppe Giaccone, MD, PhD, Principal investigator		Ph: 301-496-4916

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937
New York
	New York
	NYU Cancer Institute at New York University Medical Center
		Marc Ballas, MD	Ph:  212-731-6645

Registry Information
Official Title		Pilot Trial of Pioglitazone in Adults Undergoing Surgical Resection of Non-small Cell Lung Cancer
Trial Start Date		2008-06-02
Trial Completion Date		2010-06-02 (estimated)
Registered in ClinicalTrials.gov		NCT00751725
Date Submitted to PDQ		2008-09-02
Information Last Verified		2008-09-10