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: October 15, 2014
Last verified: February 2013

April 23, 2011
October 15, 2014
April 2011
December 2012   (final data collection date for primary outcome measure)
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.
Percent in the reduction of Ki67 expression from baseline (pre-treatment biopsy) to post-intervention (resected tumor sample) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01342770 on ClinicalTrials.gov Archive Site
  • 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.
  • Changes in the expression levels of apoptosis (caspase-3, cyclin D1, p21/Waf1, PPARγ, and MUC1) pre- and post-treatment intervention [ Designated as safety issue: No ]
  • Clinical response rates according to RECIST 1.1 [ Designated as safety issue: No ]
  • Proportion of patients with clinical and pathologic response as assessed by FDG-PET [ Designated as safety issue: No ]
  • Safety and adverse events of pioglitazone hydrochloride as assessed by NCI CTCAE v. 4.0 [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Pioglitazone Hydrochloride in Treating Patients With Stage IA-IIIA Non-small Cell Lung Cancer
Pioglitazone Hydrochloride in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer

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.

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.

Interventional
Not Provided
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
Experimental: Treatment (pioglitazone hydrochloride)
Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Interventions:
  • Drug: pioglitazone hydrochloride
  • Other: laboratory biomarker analysis
  • Other: quality-of-life assessment
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
30
February 2013
December 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01342770
NCI-2011-03826, NCI-2011-03826, CDR0000699459, MAYO-MAY10-15-02, MAY10-15-02, N01CN35000, P30CA015083
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Dennis Wigle Mayo Clinic
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP