Pioglitazone Hydrochloride in Treating Patients With Stage IA-IIIA Non-Small Cell Lung Cancer

This study has been terminated.
(The protocol has been completed prematurely due to slow accrual and budget issues.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01342770
First received: April 23, 2011
Last updated: July 9, 2013
Last verified: March 2013
  Purpose

This pilot clinical trial is studying how well pioglitazone works in treating patients with stage IA-IIIA non-small cell lung cancer. Pioglitazone hydrochloride may slow the growth of tumor cells and may be an effective treatment for non-small cell lung cancer


Condition Intervention
Stage IA Non-small Cell Lung Cancer
Stage IB Non-small Cell Lung Cancer
Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Drug: pioglitazone hydrochloride
Other: laboratory biomarker analysis
Procedure: quality-of-life assessment

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pioglitazone Hydrochloride in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in Ki-67 by IHC [ Time Frame: From baseline to post-resection ] [ Designated as safety issue: No ]
    Descriptive statistics will be used to summarize participant characteristics and all biomarker expression data. Changes in the expression levels of Ki-67 will be plotted graphically, and percent change in expression levels will be formally assessed using the paired t-test or the Wilcoxon signed rank test, if the assumptions of the t-test (i.e. normality) are not met. Changes in the IHC grades of Ki-67 expression from baseline to postintervention will be assessed using a McNemar's test.


Secondary Outcome Measures:
  • Safety as assessed by Common Terminology for Adverse Events (CTCAE) version 4.0 [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: April 2011
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pioglitazone hydrochloride)
Patients receive pioglitazone hydrochloride orally once daily for 14-42 days. Patients then undergo surgery.
Drug: pioglitazone hydrochloride
Given orally
Other Names:
  • Actos
  • pioglitazone
Other: laboratory biomarker analysis
Correlative studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the mechanism(s) of action of pioglitazone as a candidate chemopreventive agent for lung cancer by investigating the effects on Ki-67 defined in non-small cell lung cancer (NSCLC) tumor tissue.

SECONDARY OBJECTIVES:

I. To determine the effects of pioglitazone on multiple markers listed below:

  • Tumor tissue: caspase-3, cyclin D1, p21/Waf1, PPARγ, MUC1.
  • Premalignant tissue: Ki-67, caspase-3, PPARγ.
  • Histologically normal tissue: Ki-67, PPARγ. II. To evaluate the toxicity and safety of pioglitazone in this patient population.

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

IV. To describe the effects of limited treatment with pioglitazone on tumor metabolic activity as determined by FDG-PET (assessed before and after a minimum of 2 weeks of treatment).

OUTLINE:

Patients receive pioglitazone hydrochloride orally once daily for 14-42 days. Patients then undergo surgery.

  Eligibility

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

Inclusion Criteria:

  • Suspected or biopsy-proven NSCLC
  • Willingness to provide biopsy tissue for correlative studies
  • Candidate for pulmonary resection; must be able to schedule >= 14 days and =< 42 days between registration and surgery to allow for treatment with pioglitazone
  • Ability to understand and the willingness to sign a written informed consent document
  • Ability and willingness to swallow oral tablets
  • Ability and willingness to undergo two bronchoscopies (before treatment and at the time of surgery)

    • For those participants who are undergoing mediastinoscopy as part of their standard-of-care, the pre-treatment bronchoscopy may be performed during the mediastinoscopy; if the participant remains eligible for definitive surgical resection after the mediastinoscopy, the participant may proceed to registration and pioglitazone treatment
  • Current or former smoker with a >= 10 pack-year smoking history
  • Women of child-bearing potential and men who agree to use adequate contraception for the duration of study participation; the effects of pioglitazone on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women must not be pregnant or lactating. Women of child-bearing potential (women considered not of childbearing potential if they are at least two years postmenopausal and/or surgically sterile) must have used adequate contraception (abstinence; barrier methods such as IUD, diaphragm with spermicidal gel, condom, or others; and hormonal methods such as birth control pills or others) since her last menses prior to study entry; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

Exclusion Criteria:

  • Receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pioglitazone
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant or lactating woman
  • Currently treated diabetes
  • Participants with >= class II NYHA congestive heart failure or history of congestive heart failure
  • Participants with >= grade 2 (moderate) edema
  • Participants currently receiving an inhibitor of CYP2C8 (gemfibrozil, ketoconazole, quercetin, trimethoprim), or an inducer of CYP2C8 (cortisol, dexamethasone, phenobarbital, rifampin), or CYP3A4 substrate
  • Prior neoadjuvant therapy for NSCLC
  • History of bladder cancer or in situ bladder cancer
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01342770

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Dennis Wigle Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01342770     History of Changes
Other Study ID Numbers: NCI-2011-03826, MAYO-MAY10-15-02, N01CN35000, CDR0000699459
Study First Received: April 23, 2011
Last Updated: July 9, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014