Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Adenocarcinoma

Pancreatic Neoplasms

Disease Progression

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Hypoglycemic Agents

Gastrointestinal Agents

Gemcitabine

Pioglitazone

Pancrelipase

Pancreatin

pioglitazone hydrochloride

laboratory biomarker analysis

questionnaire administration

quality-of-life assessment

Yull E. Arriaga, MD

RATIONALE: Pioglitazone may slow the growth of tumor cells and may be an effective treatment for pancreatic cancer.

PURPOSE: This phase I trial is studying how well pioglitazone works as second-line therapy in treating patients with metastatic pancreatic cancer that progressed after treatment with gemcitabine.

OBJECTIVES:

Primary

* To describe changes in markers of insulin resistance, including serum adiponectin levels, standard glucose tolerance testing, and fasting serum glucose and insulin levels, in patients with previously treated metastatic adenocarcinoma of the pancreas treated with pioglitazone hydrochloride as second-line therapy.
* To describe changes in weight in these patients.
* To describe changes in ECOG performance status in these patients.
* To describe changes in symptoms and quality of life of these patients using the validated FACT-Hep scale version 4 questionnaire.

Secondary

* To determine the tumor response as measured by RECIST criteria in these patients.
* To determine the time to disease progression in these patients.

OUTLINE: Patients receive oral pioglitazone hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients complete a quality-of-life questionnaire at baseline, every 4 weeks during therapy, and then at the completion of therapy.

Patients undergo blood sample collection at baseline, every 4 weeks during therapy, and then at the completion of therapy for laboratory biomarker studies. Samples are analyzed for levels of insulin resistance markers (adiponectin, glucose, and insulin).

After completion of study therapy, patients are followed monthly for 6 months and then every 3 months for 2 years.

Pioglitazone as Second-Line in Patients With Metastatic Pancreatic Cancer After Treatment With Gemcitabine

A Pilot Study of Pioglitazone as Second Line Therapy for Patients With Previously Treated Metastatic Adenocarcinoma of the Pancreas With Disease Progression After Gemcitabine Based Chemotherapy

University of Texas Southwestern Medical Center

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

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

Laboratory Biomarker Analysis

Pioglitazone Hydrochloride

Quality-of-Life Assessment

Paul Limburg

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.

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.

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

Pioglitazone as a Candidate Chemoprevention Agent for Lung Cancer: A Pilot Trial Using a Pre-surgical Model in Early Stage NSCLC

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 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.

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.

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.

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.

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.

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.

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

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

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

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

National Cancer Institute (NCI)

Treatment (Pioglitazone Hydrochloride)

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

0=Asymptomatic and fully active

1=Symptomatic and fully ambulatory

Baseline Eastern Cooperative Oncology Group (ECOG) performance status

Former

Current

Smoking Status

Participants who met eligibility criteria that were registered and received study agent.

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

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

Percent Change in Ki-67 by Immunohistochemistry (IHC)

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

Change in Apoptosis Assessment (e.g., Caspase-3)

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

Change in Levels of Serum CA-153

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

Change in Levels of Serum CRP

Gene Expression Analysis of RNA From Bronchial Brush Cells

No Adverse Events

Grade 1 Adverse Events

Includes all registered eligible participants

Incidence of Adverse Events Graded According to Common Terminology Criteria for Adverse Events Version 4.0

Number of Participants With Clinical Response, Based on Response Evaluation Criteria in Solid Tumors ( RECIST) Version 1.1

Complete Response

No Response

Number of Participants With Complete Pathologic Response

Percent Change in Cyclin D1

Percent Change in MUC1

Percent Change in p21

Percent Change in PPARy

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

Percent Change in SUVmax From the PET Scan

Pre-intervention SUV of PET Scan

Post-intervention SUV of PET Scan

Overall Study

Mouth and Tooth Diseases

Precancerous Conditions

Leukoplakia

Leukoplakia, Oral

Pathological Conditions, Anatomical

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Leukoplakia

Oral Cancer

Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks

Three (3) placebo capsules by mouth once daily for 24 weeks

Three (3) pioglitazone 15 mg capsules by mouth once daily for 24 weeks (+/- 1 week)

Pioglitazone hydrochloride

Three (3) pioglitazone placebo capsules by mouth once daily for 24 weeks (+/- 1 week)

placebo

Powel H. Brown

The goal of this clinical research study is to learn how Actos (pioglitazone) may affect oral premalignant lesions (OPLs) and/or the risk of mouth cancer. The safety of this drug will also be studied.

PRIMARY OBJECTIVES:

I. To determine the clinical and histologic response of oral premalignant lesions to 24 weeks of therapy with pioglitazone, 45 mg once daily (qd), defined as 50% or greater reduction in the sum of all measured products of perpendicular dimensions of target lesions, or improvement in the degree of dysplasia or hyperplasia.

SECONDARY OBJECTIVES:

I. To determine the degree of change of putative biomarkers of pioglitazone efficacy including (but not restricted to) and in order of priority, tissue levels of:

* PPAR gamma,
* cyclin D1 and p21 as indirect measures of pharmacological effect
* TUNEL for apoptosis and Ki-67 for proliferation
* transglutaminase and involucrin as markers of squamous differentiation
* 15-PGDH, loss of heterozygosity (LOH). II. To determine the degree of change of C-reactive protein (CRP) in plasma. III. To assess tobacco and alcohol use among trial participants and to examine the relationship of tobacco and alcohol use to treatment response.

IV. To assess the safety of this agent in this population.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive pioglitazone hydrochloride orally (PO) once daily (QD) for 24 weeks.

ARM II: Patients receive placebo PO QD for 24 weeks.

After completion of study treatment, patients are followed up for 2 weeks.

Pioglitazone for Oral Premalignant Lesions

Phase IIB Randomized, Placebo Controlled Trial of Pioglitazone for Oral Premalignant Lesions an Inter-consortium Collaborative Study

Overall Dichotomized Clinical and Histologic Response defined as 50% or greater reduction in sum of the measured products of perpendicular dimensions of the target lesion(s) or improvement in the degree of dysplasia or hyperplasia where complete (CR) or partial response (PR) in either clinical or histologic outcome assessed according to criteria given recorded as Response or No Response and analyzed as a dichotomous variable. Clinical Response = CR: Disappearance all evidence target \& non-target lesions; PR: \>/=50% reduction in sum products of diameters all target lesion(s). Non-target lesions may not increase \>/=25% in size \& no new lesion. Histologic Response = CR: Complete reversal of dysplasia or hyperplasia to normal epithelium in all biopsied lesions. PR: Improvement of degree of dysplasia or hyperplasia in all biopsied lesion(s) from advanced to early, or from early to normal epithelium in some lesions while other biopsied lesions remain stable.

HR according to criteria \& recorded as Response or No Response, analyzed as dichotomous variable. CR: Complete reversal dysplasia/hyperplasia to normal epithelium in all biopsied lesions. PR: Improvement of degree dysplasia/hyperplasia in all biopsied lesion from advanced to early, or from early to normal epithelium in some lesions while other biopsied lesions remain stable. No Change (NC): No change in degree dysplasia/hyperplasia in all biopsied lesions, anything not CR, PR or PD. Progressive Disease (PD): Any increase in severity histology grade any biopsied lesion. Early premalignant lesion: lesion defined high risk, indicated by presence of one: hyperplasia at high-risk sites (dorsal, lateral or ventral tongue, or floor of mouth) ONLY, or mild dysplasia. Advanced premalignant lesion: lesion with presence of one: moderate dysplasia or severe dysplasia (excluding CIS), erythroplakia with hyperplasia or of any severity of dysplasia.

Clinical Response assessed according to criteria \& recorded as Response or No Response, analyzed as dichotomous variable. Complete Response (CR): Disappearance of all evidence of target AND non-target lesions. Partial Response (PR): greater than or equal to 50% reduction in the sum of the products of diameters of all target lesion(s). Non-target lesions may not increase greater than or equal 25% in size and no new lesion may appear. No Change (NC): No change in the size of the lesion(s) and no new lesions appearing, i.e. anything that is not CR, PR or PD. Progressive Disease (PD): Any increase greater than or equal to 25% in the product of the diameters of any measurable lesions or in the estimated size of non-measurable lesions or the appearance of an unequivocal new lesion.

Degree of change of C-reactive protein (CRP) in plasma serum via blood tests.

The longitudinal regression models for analysis of the change in CRP in plasma used, with suitable transformation if necessary to satisfy the model assumptions, with treatment, stage and biomarker value at screening visit as covariates.

The longitudinal regression models for analysis of the change in CRP in plasma will be used, with suitable transformation if necessary to satisfy the model assumptions, with treatment, stage and biomarker value at screening visit as covariates.

Tobacco use summarized by treatment stratified by stage and by group. In addition, the effects of tobacco and alcohol use on the primary endpoint of clinical response assessed.

Alcohol use will be summarized by treatment stratified by stage and by group. In addition, the effects of tobacco and alcohol use on the primary endpoint of clinical and pathological response assessed using statistical regression models in an exploratory fashion. Heavy drinkers are participants who drank every day; Light drinkers are participants who drank on some days; Non-drinkers are former drinkers or those who never drank alcohol.

All adverse events (including serious) and clinical laboratory toxicity summarized affected organ system. Reporting based on the NCI CTCAE v4.0 by treatment, details included in later Adverse Event Module of results.

Tissue levels of Cyclin D1 as indirect measures of pharmacological effect assessed by immunohistochemistry (IHC). Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported as percentage of cells staining positive, according to nuclear or cytoplasmic compartments.

Tissue levels of Ki-67 for proliferation assessed by immunohistochemistry (IHC). Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported as percentage of cells staining positive, according to nuclear or cytoplasmic compartments.

Tissue levels of p21 as indirect measures of pharmacological effect assessed by immunohistochemistry (IHC). Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported as percentage of cells staining positive, according to nuclear or cytoplasmic compartments.

Tissue levels of Bcl2 as indirect measures of pharmacological effect assessed by immunohistochemistry (IHC). Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported a percentage of cells staining positive, according to nuclear or cytoplasmic compartments.

Tissue levels of Peroxisome proliferator-activated receptor gamma (PPARG) Nucleus and PPARG Cytoplasm as indirect measures of pharmacological effect, PPAR gamma assessed by immunohistochemistry. Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported as percentage of cells staining positive, according to nuclear or cytoplasmic compartments.

Study source vocabulary for the study began as CTCAE version 3.0 and was translated to version 4.0.

Arm I (Pioglitazone Hydrochloride)

Arm II (Placebo)

Total

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Italy

Heavy

Light

Non-Drinker

Heavy drinkers are participants who drank every day; Light drinkers are participants who drank on some days; Non-drinkers are former drinkers or those who never drank alcohol.

Alcohol Use at Baseline

Never

Smoking Use at Baseline

University of Texas MD Anderson Phase I/II Prevention Consortium

Response

All participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug.

Overall Response <Clinical and Histologic Response Defined as 50% or Greater Reduction in the Sum of the Measured Products of Perpendicular Dimensions of the Target Lesion(s) or Improvement in the Degree of Dysplasia or Hyperplasia>

Measure at baseline, followed by Pioglitazone treatment three 15 mg capsules orally/day for 24 weeks

Pioglitazone: CRP>5 at Baseline

Measure at end of Pioglitazone treatment, approximately 24 weeks

Pioglitazone: CRP>5 End of Study

Measure at baseline, followed by Placebo treatment three capsules orally/day for 24 weeks

Placebo: CRP> 5 Baseline

Measure at end of Placebo treatment, approximately 24 weeks

Placebo: CRP>5 End of Study

Pioglitazone's 26 had 24 evaluable specimens at baseline \& 20 evaluable at end of study with 2 of those not available for CRP\>5 baseline measure: Placebo's 25 had 25 evaluable specimens at baseline \& 21 at end of study. Analysis based on specimen viability/availability, no exclusions made for other reasons, participant needed 1/+ dose of treatment.

Number of Participants With >5.0 mg/L in Level of C-reactive Protein in Plasma

Pioglitazone's 26 had 20 evaluable specimens at baseline \& 20 at end of study with 2 of those not available for the CRP\>5 baseline measure \& Placebo's 25 had 25 evaluable at baseline \& 21 evaluable at end of study. Analysis based on specimen viability/availability, no exclusions made for other reasons, participants needed 1/+ dose of treatment.

Number of Participants With Level of C-reactive Protein in Plasma Decrease From >5.0 mg/L to <= 5.0 mg/L From Baseline to End of Study

Never Smoked

Former Smoker

Current Smoker

Analysis includes all participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug.

Number of Participant With Clinical Response by Baseline Characteristics: Tobacco Use

Light Drinker

Heavy Drinker

Number of Participant With Clinical Response by Baseline Characteristics: Alcohol Use

Blood & Lymphatic System Disorders

Cardiac Disorders

Ear & Labyrinth Disorders

Eye Disorders

Gastrointestinal Disorders

General Disorders & Administration Site Conditions

Infections and Infestations

Injury, Poisoning and Procedural Complications

Investigations

Metabolism and Nutrition Disorders

Musculoskeletal and Connective Tissue Disorders

Neoplasms Benign, Malignant and Unspecified

Nervous System Disorders

Psychiatric Disorders

Reproductive System and Breast Disorders

Respiratory, Thoracic and Mediastinal Disorders

Skin and Subcutaneous Tissue Disorders

Surgical and Medical Procedures

Vascular Disorders

Population includes all enrolled participants.

Number of Participants Affected by Adverse Events Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4.0)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pioglitazone as Second-Line in Patients With Metastatic Pancreatic Cancer After Treatment With Gemcitabine	NCT00867126	Pancreatic Canc...	pioglitazone hy... laboratory biom... questionnaire a... quality-of-life...	18 Years - 120 Years	University of Texas Southwestern Medical Center
Pioglitazone Hydrochloride in Treating Patients With Stage IA-IIIA Non-small Cell Lung Cancer	NCT01342770	Stage IA Non-Sm... Stage IB Non-Sm... Stage IIA Non-S... Stage IIB Non-S... Stage IIIA Non-...	Laboratory Biom... Pioglitazone Hy... Quality-of-Life...	18 Years -	National Cancer Institute (NCI)
Pioglitazone as Second-Line in Patients With Metastatic Pancreatic Cancer After Treatment With Gemcitabine	NCT00867126	Pancreatic Canc...	pioglitazone hy... laboratory biom... questionnaire a... quality-of-life...	18 Years - 120 Years	University of Texas Southwestern Medical Center
Pioglitazone for Oral Premalignant Lesions	NCT00951379	Oral Leukoplaki...	Pioglitazone hy... placebo laboratory biom...	18 Years -	National Cancer Institute (NCI)
Pioglitazone Hydrochloride in Treating Patients With Stage IA-IIIA Non-small Cell Lung Cancer	NCT01342770	Stage IA Non-Sm... Stage IB Non-Sm... Stage IIA Non-S... Stage IIB Non-S... Stage IIIA Non-...	Laboratory Biom... Pioglitazone Hy... Quality-of-Life...	18 Years -	National Cancer Institute (NCI)
Pioglitazone for Oral Premalignant Lesions	NCT00951379	Oral Leukoplaki...	Pioglitazone hy... placebo laboratory biom...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for pioglitazone hydrochloride