Trial Outcomes & Findings for Pioglitazone Hydrochloride in Treating Patients With Stage IA-IIIA Non-small Cell Lung Cancer (NCT NCT01342770)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Baseline and at the time of surgery, after 42 days of treatment

Results posted on

2017-12-05

Participant Flow

Ten subjects were pre-registered at one Cancer Prevention Network (CPN) member organization from 2011 to 2013.

Four participants were deemed screen failures (3 without histologically-confirmed non-small cell lung cancer (NSCLC) and 1 with metastatic NSCLC and were excluded from all analyses.

Participant milestones

Participant milestones
Measure	Treatment (Pioglitazone Hydrochloride) Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Pioglitazone Hydrochloride) n=6 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Age, Continuous	64 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) performance status 0=Asymptomatic and fully active	5 participants n=5 Participants
Baseline Eastern Cooperative Oncology Group (ECOG) performance status 1=Symptomatic and fully ambulatory	1 participants n=5 Participants
Smoking Status Former	4 participants n=5 Participants
Smoking Status Current	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and at the time of surgery, after 42 days of treatment

Population: Includes all registered participants with pre- and post-intervention tumor tissue samples except one participant who was deemed ineligible post-registration

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.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=5 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Percent Change in Ki-67 by Immunohistochemistry (IHC)	-20.0 Percent change in Ki-67 measurements Interval -40.0 to -11.1

SECONDARY outcome

Timeframe: Baseline and at the time of surgery, after 42 days of treatment

Population: Data were not collected. Study team decision not to analyze this endpoint.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and at the time of surgery, after 42 days of treatment

Population: Data were not collected due to a study team decision not to analyze this endpoint.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and at the time of surgery, after 42 days of treatment

Population: Data not collected due to a study team decision not to analyze this endpoint.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to the time of surgery, after 42 days of treatment

Population: Data not collected due to a study team decision not to analyze this endpoint.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to the time of surgery, after 42 days of treatment

Population: Includes all registered eligible participants

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.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=5 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events Version 4.0 No Adverse Events	3 participants
Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events Version 4.0 Grade 1 Adverse Events	2 participants

SECONDARY outcome

Timeframe: Up to the time of surgery, after 42 days of treatment

Population: Data not collected due to a study team decision not to analyze this endpoint.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to the time of surgery, after 42 days of treatment

Population: Includes all registered participants

Complete pathologic response was defined as no viable residual tumor cells. Acellular residual mucin pools also considered a pathologic complete response.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=6 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Number of Participants With Complete Pathologic Response Complete Response	1 participants
Number of Participants With Complete Pathologic Response No Response	5 participants

SECONDARY outcome

Timeframe: Baseline to the time of surgery, after 42 days of treatment

Population: Includes all registered participants with pre- and post-intervention tumor tissue samples except one participant who was deemed ineligible post-registration

Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=5 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Percent Change in Cyclin D1	-69 Percent change in Cyclin D1 measurements Interval -91.0 to 50.0

SECONDARY outcome

Timeframe: Baseline to the time of surgery, after 42 days of treatment

Population: Includes all registered participants with pre- and post-intervention tumor tissue samples except one participant who was deemed ineligible post-registration

Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=5 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Percent Change in MUC1	0 Percent change in MUC1 measurements Interval -16.7 to 40.0

SECONDARY outcome

Timeframe: Baseline to the time of surgery, after 42 days of treatment

Population: Includes all registered participants with pre- and post-intervention tumor tissue samples except one participant who was deemed ineligible post-registration

Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=5 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Percent Change in p21	-5 Percent change in p21 measurements Interval -88.9 to 50.0

SECONDARY outcome

Timeframe: Baseline to the time of surgery, after 42 days of treatment

Population: Includes all registered participants with pre- and post-intervention tumor tissue samples except one participant who was deemed ineligible post-registration

Changes in the expression levels from baseline (prior to intervention) to post intervention (resected tumor sample) will be plotted graphically.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=5 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Percent Change in PPARy	183.4 Percent change in PPARy measurements Interval 0.0 to 1100.0

SECONDARY outcome

Timeframe: Baseline to the time of surgery, after 42 days of treatment

Population: Includes registered eligible participants with pre- and post-intervention PET/CT images obtained

The percent change from pre to post-intervention in SUV max values will be summarized using descriptive statistics and simple graphical plots.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=3 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Percent Change in SUVmax From the PET Scan	0 Percent change in tumor SUV max values Interval -15.4 to 0.0

SECONDARY outcome

Timeframe: Baseline

Population: Includes registered eligible participants with pre- and post-intervention PET/CT images obtained

The pre- and post-intervention SUV will be summarized using descriptive statistics and simple graphical plots.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=3 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Pre-intervention SUV of PET Scan	13.0 SUV Interval 12.2 to 18.7

SECONDARY outcome

Timeframe: Time of surgery, after 42 days of treatment

Population: Includes registered eligible participants with pre- and post-intervention PET/CT images obtained

The pre- and post-intervention SUV will be summarized using descriptive statistics and simple graphical plots.

Outcome measures

Outcome measures
Measure	Treatment (Pioglitazone Hydrochloride) n=3 Participants Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Post-intervention SUV of PET Scan	12.2 SUV Interval 11.0 to 18.7

Adverse Events

Treatment (Pioglitazone Hydrochloride)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment (Pioglitazone Hydrochloride) n=5 participants at risk Patients receive pioglitazone hydrochloride PO QD for 14-42 days. Patients then undergo surgery.
Gastrointestinal disorders Oral Pain	20.0% 1/5 • Number of events 1
Nervous system disorders Tremor	20.0% 1/5 • Number of events 1
Gastrointestinal disorders Hemorrhoidal Hemorrhage	20.0% 1/5 • Number of events 1
Infections and infestations Lung Infection	20.0% 1/5 • Number of events 1

Additional Information

Dennis Wigle, M.D., Ph.D.

Mayo Clinic

Phone: 507-284-2511

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60