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

Primary Purpose

Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma, Stage IIA Non-Small Cell Lung Carcinoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Pioglitazone Hydrochloride
Quality-of-Life Assessment
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage IA Non-Small Cell Lung Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (pioglitazone hydrochloride)

Arm Description

Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.

Outcomes

Primary Outcome Measures

Percent Change in Ki-67 by Immunohistochemistry (IHC)
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.

Secondary Outcome Measures

Change in Apoptosis Assessment (e.g., Caspase-3)
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 Levels of Serum CA-153
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
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.
Gene Expression Analysis of RNA From Bronchial Brush Cells
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.
Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events Version 4.0
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.
Number of Participants With Clinical Response, Based on Response Evaluation Criteria in Solid Tumors ( RECIST) Version 1.1
Clinical response rates will be summarized. Complete response (CR) is the disappearance of all non-nodal target lesions (TL) and each target lymph node (LN) must have reduction in short axis to <1.0cm. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameters (LD) of the non-nodal TR and the short axis of the target LN with the baseline sum diameters (BSD) as reference. Progression (PD) is at least 1 new malignant lesion or LN whose short axis increased to >1.5 cm or at least a 20% increase in the sum of TL diameters with the minimum sum of diameters as reference.
Number of Participants With Complete Pathologic Response
Complete pathologic response was defined as no viable residual tumor cells. Acellular residual mucin pools also considered a pathologic complete response.
Percent Change in Cyclin D1
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Percent Change in MUC1
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Percent Change in p21
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Percent Change in PPARy
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Percent Change in SUVmax From the PET Scan
The percent change from pre to post-intervention in SUV max values will be summarized using descriptive statistics and simple graphical plots.
Pre-intervention SUV of PET Scan
The pre- and post-intervention SUV will be summarized using descriptive statistics and simple graphical plots.
Post-intervention SUV of PET Scan
The pre- and post-intervention SUV will be summarized using descriptive statistics and simple graphical plots.

Full Information

First Posted
April 23, 2011
Last Updated
October 30, 2017
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01342770
Brief Title
Pioglitazone Hydrochloride in Treating Patients With Stage IA-IIIA Non-small Cell Lung Cancer
Official Title
Pioglitazone as a Candidate Chemoprevention Agent for Lung Cancer: A Pilot Trial Using a Pre-surgical Model in Early Stage NSCLC
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Terminated
Study Start Date
April 2011 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot phase II 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma, Stage IIA Non-Small Cell Lung Carcinoma, Stage IIB Non-Small Cell Lung Carcinoma, Stage IIIA Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (pioglitazone hydrochloride)
Arm Type
Experimental
Arm Description
Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Pioglitazone Hydrochloride
Other Intervention Name(s)
Actos, Pioglitazone.HCl
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Percent Change in Ki-67 by Immunohistochemistry (IHC)
Description
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.
Time Frame
Baseline and at the time of surgery, after 42 days of treatment
Secondary Outcome Measure Information:
Title
Change in Apoptosis Assessment (e.g., Caspase-3)
Description
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.
Time Frame
Baseline and at the time of surgery, after 42 days of treatment
Title
Change in Levels of Serum CA-153
Description
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.
Time Frame
Baseline and at the time of surgery, after 42 days of treatment
Title
Change in Levels of Serum CRP
Description
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.
Time Frame
Baseline and at the time of surgery, after 42 days of treatment
Title
Gene Expression Analysis of RNA From Bronchial Brush Cells
Description
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.
Time Frame
Up to the time of surgery, after 42 days of treatment
Title
Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events Version 4.0
Description
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.
Time Frame
Up to the time of surgery, after 42 days of treatment
Title
Number of Participants With Clinical Response, Based on Response Evaluation Criteria in Solid Tumors ( RECIST) Version 1.1
Description
Clinical response rates will be summarized. Complete response (CR) is the disappearance of all non-nodal target lesions (TL) and each target lymph node (LN) must have reduction in short axis to <1.0cm. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameters (LD) of the non-nodal TR and the short axis of the target LN with the baseline sum diameters (BSD) as reference. Progression (PD) is at least 1 new malignant lesion or LN whose short axis increased to >1.5 cm or at least a 20% increase in the sum of TL diameters with the minimum sum of diameters as reference.
Time Frame
Up to the time of surgery, after 42 days of treatment
Title
Number of Participants With Complete Pathologic Response
Description
Complete pathologic response was defined as no viable residual tumor cells. Acellular residual mucin pools also considered a pathologic complete response.
Time Frame
Up to the time of surgery, after 42 days of treatment
Title
Percent Change in Cyclin D1
Description
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Time Frame
Baseline to the time of surgery, after 42 days of treatment
Title
Percent Change in MUC1
Description
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Time Frame
Baseline to the time of surgery, after 42 days of treatment
Title
Percent Change in p21
Description
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Time Frame
Baseline to the time of surgery, after 42 days of treatment
Title
Percent Change in PPARy
Description
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Time Frame
Baseline to the time of surgery, after 42 days of treatment
Title
Percent Change in SUVmax From the PET Scan
Description
The percent change from pre to post-intervention in SUV max values will be summarized using descriptive statistics and simple graphical plots.
Time Frame
Baseline to the time of surgery, after 42 days of treatment
Title
Pre-intervention SUV of PET Scan
Description
The pre- and post-intervention SUV will be summarized using descriptive statistics and simple graphical plots.
Time Frame
Baseline
Title
Post-intervention SUV of PET Scan
Description
The pre- and post-intervention SUV will be summarized using descriptive statistics and simple graphical plots.
Time Frame
Time of surgery, after 42 days of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Limburg
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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

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