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

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00751725

Purpose

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.

Condition	Intervention	Phase
Lung Cancer	Drug: pioglitazone hydrochloride Procedure: TdT-mediated dUTP nick end labeling assay Procedure: immunohistochemistry staining method Procedure: laboratory biomarker analysis Procedure: therapeutic conventional surgery	Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	Pilot Trial of Pioglitazone in Adults Undergoing Surgical Resection of Non-Small Cell Lung Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Effect of pioglitazone hydrochloride on the apoptotic index in tumor tissue as assessed by TUNEL assay [ Designated as safety issue: No ]

Secondary Outcome Measures:

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) [ Designated as safety issue: No ]
Effect of pioglitazone hydrochloride on histologically normal bronchial epithelial tissue biomarkers (i.e., Ki-67 and PPARγ) [ Designated as safety issue: No ]
Effect of pioglitazone hydrochloride on premalignant bronchial epithelial tissue biomarkers (i.e., Ki-67, apoptotic index, and PPARγ) [ Designated as safety issue: No ]
Effect of pioglitazone hydrochloride on serum biomarkers (i.e., C-reactive protein, CA15-3, CEA, and CA-125) [ Designated as safety issue: No ]
Clinical response as assessed by FDG-PET in a subset of patients receiving treatment at the National Cancer Institute [ Designated as safety issue: No ]
Clinical toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	25
Study Start Date:	June 2008
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00751725

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937
United States, New York
NYU Cancer Institute at New York University Medical Center	Recruiting
New York, New York, United States, 10016
Contact: Marc Ballas, MD 212-731-6645

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Giuseppe Giaccone, MD, PhD

NCI - Medical Oncology Branch

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000614259, NCI-08-C-0208
Study First Received:	September 11, 2008
Last Updated:	December 11, 2008
ClinicalTrials.gov Identifier:	NCT00751725
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I non-small cell lung cancer
stage II non-small cell lung cancer

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Pioglitazone
Respiratory Tract Diseases
Lung Neoplasms

Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Respiratory Tract Neoplasms
Neoplasms
Hypoglycemic Agents
Neoplasms by Site

Neoplasms by Histologic Type
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009