Stage IA Non-Small Cell Lung CarcinomaPhase 2NCT01342770
Pioglitazone Hydrochloride in Treating Patients With Stage IA-IIIA Non-small Cell Lung Cancer
A Phase 2 study testing Laboratory Biomarker Analysis, Pioglitazone Hydrochloride and Quality-of-Life Assessment in people with Stage IA Non-Small Cell Lung Carcinoma and Stage IB Non-Small Cell Lung Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IA Non-Small Cell Lung Carcinoma, Stage IB Non-Small Cell Lung Carcinoma, Stage IIA Non-Small Cell Lung Carcinoma
- What is being tested?
- Laboratory Biomarker Analysis, Pioglitazone Hydrochloride and Quality-of-Life Assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Feb 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pioglitazone as a Candidate Chemoprevention Agent for Lung Cancer: A Pilot Trial Using a Pre-surgical Model in Early Stage NSCLC
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- 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
- Being tested
- Laboratory Biomarker Analysis, Pioglitazone Hydrochloride, Quality-of-Life Assessment
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Pioglitazone HydrochlorideDrug
Also called Actos, Pioglitazone.HCl
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pioglitazone hydrochloride) | Experimental | Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery. Receives: Other: Laboratory Biomarker Analysis; Drug: Pioglitazone Hydrochloride; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and at the time of surgery, after 42 days of treatment
Secondary outcomes (14)
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.
Measured: Baseline and at the time of surgery, after 42 days of treatment
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.
Measured: Baseline and at the time of surgery, after 42 days of treatment
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.
Measured: Baseline and at the time of surgery, after 42 days of treatment
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.
Measured: Up to the time of surgery, after 42 days of treatment
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.
Measured: Up to the time of surgery, after 42 days of treatment
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.
Measured: Up to the time of surgery, after 42 days of treatment
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.
Measured: Up to the time of surgery, after 42 days of treatment
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.
Measured: Baseline to the time of surgery, after 42 days of treatment
Percent Change in MUC1
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Measured: Baseline to the time of surgery, after 42 days of treatment
Percent Change in p21
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Measured: Baseline to the time of surgery, after 42 days of treatment
Percent Change in PPARy
Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.
Measured: Baseline to the time of surgery, after 42 days of treatment
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.
Measured: Baseline to the time of surgery, after 42 days of treatment
Pre-intervention SUV of PET Scan
The pre- and post-intervention SUV will be summarized using descriptive statistics and simple graphical plots.
Measured: Baseline
Post-intervention SUV of PET Scan
The pre- and post-intervention SUV will be summarized using descriptive statistics and simple graphical plots.
Measured: Time of surgery, after 42 days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2011 (estimated)
- Study startApr 2011
- Primary completionDec 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stage IA Non-Small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Paul Limburg, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01342770
- Sponsor's protocol ID
- NCI-2011-03826
- Other IDs
- NCI-2011-03826, MAYO-MAY10-15-02, N01-CN-2012-00042, CDR0000699459, MAY10-15-02, MAY10-15-02, N01CN00042, N01CN35000
- Status last verified
- Oct 2017
- First submitted
- 23 Apr 2011
- Last updated
- 5 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pioglitazone as a Candidate Chemoprevention Agent for Lung Cancer: A Pilot Trial Using a Pre-surgical Model in Early Stage NSCLC
- ClinicalTrials.gov ID
- NCT01342770
- Acronym / sponsor ID
- NCI-2011-03826
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 27 Apr 2011 (estimated)
- Results
- Posted 6 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pioglitazone hydrochloride) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Pioglitazone Hydrochloride, Other: Quality-of-Life AssessmentPatients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pioglitazone hydrochloride) |
| Pioglitazone HydrochlorideAlso: Actos, Pioglitazone.HClGiven PO | Drug | Treatment (pioglitazone hydrochloride) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (pioglitazone hydrochloride) |
Primary outcome
Percent Change in Ki-67 by Immunohistochemistry (IHC)
Time frame: Baseline and at the time of surgery, after 42 days of treatment
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.
14 secondary outcomes
Change in Apoptosis Assessment (e.g., Caspase-3)
Time frame: Baseline and at the time of surgery, after 42 days of treatment
Change in Levels of Serum CA-153
Time frame: Baseline and at the time of surgery, after 42 days of treatment
Change in Levels of Serum CRP
Time frame: Baseline and at the time of surgery, after 42 days of treatment
Gene Expression Analysis of RNA From Bronchial Brush Cells
Time frame: Up to the time of surgery, after 42 days of treatment
Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events Version 4.0
Time frame: Up to the time of surgery, after 42 days of treatment
Number of Participants With Clinical Response, Based on Response Evaluation Criteria in Solid Tumors ( RECIST) Version 1.1
Time frame: Up to the time of surgery, after 42 days of treatment
Number of Participants With Complete Pathologic Response
Time frame: Up to the time of surgery, after 42 days of treatment
Percent Change in Cyclin D1
Time frame: Baseline to the time of surgery, after 42 days of treatment
Percent Change in MUC1
Time frame: Baseline to the time of surgery, after 42 days of treatment
Percent Change in p21
Time frame: Baseline to the time of surgery, after 42 days of treatment
Percent Change in PPARy
Time frame: Baseline to the time of surgery, after 42 days of treatment
Percent Change in SUVmax From the PET Scan
Time frame: Baseline to the time of surgery, after 42 days of treatment
Pre-intervention SUV of PET Scan
Time frame: Baseline
Post-intervention SUV of PET Scan
Time frame: Time of surgery, after 42 days of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Limburg principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis, Pioglitazone Hydrochloride and Quality-of-Life Assessment in people with Stage IA Non-Small Cell Lung Carcinoma and Stage IB Non-Small Cell Lung Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Ki-67 by Immunohistochemistry (IHC) (time frame: Baseline and at the time of surgery, after 42 days of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2017.