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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01342770
First received: April 23, 2011
Last updated: November 13, 2014
Last verified: February 2013
  Purpose

This pilot clinical trial studies 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 Phase
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
Other: quality-of-life assessment
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pioglitazone as a Candidate Chemoprevention Agent for Lung Cancer: A Pilot Trial Using a Pre-surgical Model in Early Stage NSCLC

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in Ki-67 by immunohistochemistry (IHC) [ Time Frame: Baseline to the time of surgery ] [ 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:
  • Change in apoptosis assessment (e.g., caspase-3) [ Time Frame: Baseline to the time of surgery ] [ Designated as safety issue: No ]
    Changes in the expression levels (or grades) from baseline (prior to intervention) to post-intervention (resected tumor sample) will be plotted graphically as well as formally assessed using the McNemar's tests (for categorical variables) or Wilcoxon signed rank tests (for continuous variables) respectively.

  • Change in cyclin D1 [ Time Frame: Baseline to the time of surgery ] [ Designated as safety issue: No ]
    Changes in the expression levels (or grades) from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically as well as formally assessed using the McNemar's tests (for categorical variables) or Wilcoxon signed rank tests (for continuous variables) respectively.

  • Change in p21 [ Time Frame: Baseline to the time of surgery ] [ Designated as safety issue: No ]
    Changes in the expression levels (or grades) from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically as well as formally assessed using the McNemar's tests (for categorical variables) or Wilcoxon signed rank tests (for continuous variables) respectively.

  • Change in PPARy [ Time Frame: Baseline to the time of surgery ] [ Designated as safety issue: No ]
    Changes in the expression levels (or grades) from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically as well as formally assessed using the McNemar's tests (for categorical variables) or Wilcoxon signed rank tests (for continuous variables) respectively.

  • Change in MUC1 [ Time Frame: Baseline to the time of surgery ] [ Designated as safety issue: No ]
    Changes in the expression levels (or grades) from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically as well as formally assessed using the McNemar's tests (for categorical variables) or Wilcoxon signed rank tests (for continuous variables) respectively.

  • Clinical response rate, calculated on a per-participant basis using RECIST 1.1 [ Time Frame: Up to the time of surgery ] [ Designated as safety issue: No ]
    The clinical response rates based on RECIST 1.1 will be summarized, and 95% binomial confidence intervals will be reported.

  • Pathologic complete response rate, defined as no viable residual tumor cells [ Time Frame: Up to the time of surgery ] [ Designated as safety issue: No ]
    The proportion of participants with complete pathologic response will be calculated, along with the corresponding 95% binomial confidence intervals.

  • Gene expression analysis of RNA from bronchial brush cells [ Time Frame: Up to the time of surgery ] [ Designated as safety issue: No ]
    For the gene expression profiles obtained from the data from normal bronchial brush cells, each participant's pre- and post gene expression will be graphically represented and the mean expression levels analyzed using a paired t-test or Wilcoxon signed rank test, if the assumptions of the t-test are not met.

  • Change in levels of serum CA-153 [ Time Frame: Baseline to the time of surgery ] [ Designated as safety issue: No ]
    Each participant's pre- and post serum levels of CA-153 will be graphically represented and the mean levels analyzed using a paired t-test or Wilcoxon signed rank test, if the assumptions of the t-test are not met.

  • Change in levels of serum CRP [ Time Frame: Baseline to the time of surgery ] [ Designated as safety issue: No ]
    Each participant's pre- and post serum levels of CRP will be graphically represented and the mean levels analyzed using a paired t-test or Wilcoxon signed rank test, if the assumptions of the t-test are not met.

  • Change in uptake from the PET scan [ Time Frame: Baseline to the time of surgery ] [ Designated as safety issue: No ]
    The pre- and post-intervention SUV and lymph node uptake of PET as well as change from pre to post-intervention will be summarized using descriptive statistics and simple graphical plots. An optimal cutpoint for the reduction in SUV and lymph node uptake values will be explored using clinical approach, as well as using data dependent methods and outcome based approaches. The percentage of participants with a clinically meaningful drop in SUV and lymph node uptake will be summarized and correlated with clinical and pathologic response.

  • Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to the time of surgery ] [ Designated as safety issue: Yes ]
    To evaluate the adverse events profile, the maximum grade for each type of adverse event will be recorded for each participant and frequency tables will be reviewed to determine the overall patterns. The number and severity of adverse events (both regardless of attribution as well as those that are at least possibly, probably, or definitely related) will be tabulated and summarized.


Enrollment: 30
Study Start Date: April 2011
Study Completion Date: February 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pioglitazone hydrochloride)
Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Drug: pioglitazone hydrochloride
Given PO
Other Names:
  • Actos
  • pioglitazone
Other: laboratory biomarker analysis
Correlative studies
Other: 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, peroxisome proliferative activated receptor, gamma (PPARγ), mucin 1 (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 (PO) once daily (QD) 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; 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 intrauterine device [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 New York Heart Association (NYHA) congestive heart failure or history of congestive heart failure
  • Participants with >= grade 2 (moderate) edema
  • Participants currently receiving an inhibitor of cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) (gemfibrozil, ketoconazole, quercetin, trimethoprim), or an inducer of CYP2C8 (cortisol, dexamethasone, phenobarbital, rifampin), or cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) substrate
  • Prior neoadjuvant therapy for NSCLC
  • History of bladder cancer or in situ bladder cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, NCI-2011-03826, CDR0000699459, MAYO-MAY10-15-02, MAY10-15-02, P30CA015083, N01CN00042, N01CN35000
Study First Received: April 23, 2011
Last Updated: November 13, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 24, 2014