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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-03152 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| UWI H-2009-0106 | |||
| MDA-2009-0339 | Other Identifier | MD Anderson Cancer Center (MDACC) | |
| INC07-10-01 | Other Identifier | DCP | |
| N01CN35159 | U.S. NIH Grant/Contract | View source | |
| N01CN35153 | U.S. NIH Grant/Contract | View source | |
| P30CA016672 | U.S. NIH Grant/Contract | View source |
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Due to slow accrual.
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I (Pioglitazone Hydrochloride) | Experimental | Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks |
|
| Arm II (Placebo) | Placebo Comparator | Three (3) placebo capsules by mouth once daily for 24 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pioglitazone hydrochloride | Drug | Three (3) pioglitazone 15 mg capsules by mouth once daily for 24 weeks (+/- 1 week) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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> | 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. | Response assessed at Week 24 ±1 Week |
| Dichotomized Histologic Response (HR): Participant Complete or Partial Response Defined as =/>50% 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 | 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. | Response assessed at Week 24 ±1 Week |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With >5.0 mg/L in Level of C-reactive Protein in Plasma | 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. | Baseline to end of study, 24 weeks |
Not provided
Inclusion Criteria:
STAGE I:
Males or females with a suspected or histologically confirmed oral premalignant lesion(s) (up to three target lesions may be followed for the purpose of the study) that has a length (longest diameter) of 8 mm or greater and width (diameter perpendicular to greatest length) of 3 mm or greater in size
The participant's life expectancy is > 6 months
The participant has discontinued any other oral cancer chemopreventive therapy at least 12 weeks prior to the baseline visit and all toxicities have been fully resolved; daily aspirin is permitted
The participant is willing and able to fully participate for the duration of the study
Women must not be pregnant or lactating; women of child-bearing potential (women are 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 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; women of child-bearing potential and men must agree to use adequate contraception for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
Ability to understand and the willingness to sign a written informed consent document
STAGE II:
The participant has one or more target lesions histologically confirmed by a biopsy obtained no more than 9 weeks prior to randomization, that is either:
An EARLY premalignant lesion defined to be at high risk:
Mild dysplasia of any site
Hyperplastic leukoplakia of a high-risk site
An ADVANCED premalignant lesion defined as the presence of at least one of the following:
Hemoglobin levels equal to or above the lower limit of normal
White blood cells >= 3,000/uL
Platelets >= 125,000/uL
Total bilirubin =< 1.5 * upper limit of normal (ULN)
BUN and serum creatinine =< 1.5 * ULN
Glucose, serum < 200 mg/dL
The participant's Eastern Cooperative Oncology Group (ECOG) performance status is 0 or 1
If the participant is female and of childbearing potential and not lactating she has a documented negative serum pregnancy test within 14 days prior to randomization
The participant has a baseline EKG that does not show signs of acute cardiac ischemia or cardiac dysrhythmia (except for 1st degree AV block or chronic atrial fibrillation); EKG can be an earlier report within 12 weeks prior to registration
Participants using the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 3 days prior to starting pioglitazone or placebo on this study; the use of the following drugs or drug classes is prohibited during pioglitazone/placebo treatment: participants taking inhibitors of CYP2C8 (gemfibrozil, ketoconazole, quercetin, trimethoprim), enzyme inducers of CYP2C8 (cortisol, dexamethasone, phenobarbital, rifampin), and CYP3A4 substrate
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Powel H. Brown | University of Texas MD Anderson Cancer Center, Consortium PI | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| University of Iowa Hospitals and Clinics |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39584361 | Derived | Gates JC, Abouyared M, Shnayder Y, Farwell DG, Day A, Alawi F, Moore M, Holcomb AJ, Birkeland A, Epstein J. Clinical Management Update of Oral Leukoplakia: A Review From the American Head and Neck Society Cancer Prevention Service. Head Neck. 2025 Feb;47(2):733-741. doi: 10.1002/hed.28013. Epub 2024 Nov 25. |
| Label | URL |
|---|---|
| University of Texas MD Anderson Cancer Center Official Website | View source |
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Of the 99 participants screened during recruitment phase, 47 participants failed screening and were excluded from the trial before assignment to groups. Due to slow accrual, the study was terminated in September 2013.
Recruitment Period: first participant accrued July 12, 2010 and the last participant accrued on September 10, 2013. Recruitment done in medical clinic settings across the United States, at the European Institute of Oncology in Milan, Italy, and at the BC Cancer Center, Vancouver, British Columbia, Canada.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm I (Pioglitazone Hydrochloride) | Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks |
| FG001 | Arm II (Placebo) | Three (3) placebo capsules by mouth once daily for 24 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| placebo | Other | Three (3) pioglitazone placebo capsules by mouth once daily for 24 weeks (+/- 1 week) |
|
|
| laboratory biomarker analysis | Other | Correlative studies |
|
| Dichotomized Clinical Response: Participant Complete or Partial Response Defined as =/>50% 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 | 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. | Response assessed at Week 24 ±1 Week |
| 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 | 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. | Baseline to end of study, 24 weeks |
| Number of Participant With Clinical Response by Baseline Characteristics: Tobacco Use | 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. | Up to 26 weeks |
| Number of Participant With Clinical Response by Baseline Characteristics: Alcohol Use | 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. | Up to 26 weeks |
| 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) | 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. | Up to 26 weeks |
| Biomarker Measurements at Scheduled Visits: Tissue Levels of Cyclin D1 | 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. | Baseline to end of study, 24 weeks |
| Biomarker Measurements at Scheduled Visits: Tissue Levels of Ki-67 | 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. | Baseline to end of study, 24 weeks |
| Biomarker Measurements at Scheduled Visits: Tissue Levels of p21 | 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. | Baseline to end of study, 24 weeks |
| Biomarker Measurements at Scheduled Visits: Tissue Levels of B-cell Lymphoma 2 (Bcl2) | 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. | Baseline to end of study, 24 weeks |
| Biomarker Measurements at Scheduled Visits: Tissue Levels of PPARG Nucleus and PPARG Cytoplasm | 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. | Baseline to end of study, 24 weeks |
| Iowa City |
| Iowa |
| 52242 |
| United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| Masonic Cancer Center, University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Roswell Park Cancer Institute | Buffalo | New York | 14263 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10065 | United States |
| Weill Medical College of Cornell University | New York | New York | 10065 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| University of Wisconsin Hospital and Clinics | Madison | Wisconsin | 53792 | United States |
| BC Cancer Agency (Vancouver Cancer Centre) | Vancouver | British Columbia | V5Z 4E6 | Canada |
| European Institute of Oncology | Milan | 20141 | Italy |
| National Cancer Institute (NCI) Central Website for Cancer Research | View source |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm I (Pioglitazone Hydrochloride) | Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks |
| BG001 | Arm II (Placebo) | Three (3) placebo capsules by mouth once daily for 24 weeks |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Alcohol Use at Baseline | 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. | Number | participants |
| |||||||||||||||
| Smoking Use at Baseline | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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> | 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. | All participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug. | Posted | Number | participants | Response assessed at Week 24 ±1 Week |
|
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With >5.0 mg/L in Level of C-reactive Protein in Plasma | 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. | 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. | Posted | Number | participants | Baseline to end of study, 24 weeks |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | 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 | 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. | 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. | Posted | Number | participants | Baseline to end of study, 24 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participant With Clinical Response by Baseline Characteristics: Tobacco Use | 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. | Analysis includes all participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug. | Posted | Number | participants | Up to 26 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participant With Clinical Response by Baseline Characteristics: Alcohol Use | 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 participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug. | Posted | Number | participants | Up to 26 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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) | 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. | Population includes all enrolled participants. | Posted | Number | participants | Up to 26 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Biomarker Measurements at Scheduled Visits: Tissue Levels of Cyclin D1 | 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. | Two participants in the Pioglitazone arm were not analyzed for Cyclin D1 end of study score. Analysis is based on specimen viability/availability. No exclusions are made for any other reason. | Posted | Mean | Standard Deviation | percentage of staining cells positive | Baseline to end of study, 24 weeks |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Biomarker Measurements at Scheduled Visits: Tissue Levels of Ki-67 | 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. | Four participants in the Pioglitazone arm were not analyzed for Ki-67 end of study score. Analysis is based on specimen viability/availability. No exclusions are made for any other reason. | Posted | Mean | Standard Deviation | percentage of staining cells positive | Baseline to end of study, 24 weeks |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Biomarker Measurements at Scheduled Visits: Tissue Levels of p21 | 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. | Two participants in the Pioglitazone arm were not analyzed for p21 end of study score. Analysis is based on specimen viability/availability. No exclusions are made for any other reason. | Posted | Mean | Standard Deviation | percentage of staining cells positive | Baseline to end of study, 24 weeks |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Biomarker Measurements at Scheduled Visits: Tissue Levels of B-cell Lymphoma 2 (Bcl2) | 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. | Four participants of 25 overall in the Pioglitazone arm were not analyzed for Bcl2 end of study score and one participant in Placebo was not analyzed for Bcl2 baseline score. Analysis is based on specimen viability/availability. No exclusions are made for any other reason. | Posted | Mean | Standard Deviation | percentage of staining cells positive | Baseline to end of study, 24 weeks |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Biomarker Measurements at Scheduled Visits: Tissue Levels of PPARG Nucleus and PPARG Cytoplasm | 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. | Four participants in the Pioglitazone arm were not analyzed at end of study, and two participants in Placebo were not analyzed for PPARG baseline scores. Analysis is based on specimen viability/availability. No exclusions are made for any other reason. | Posted | Mean | Standard Deviation | percentage of staining cells positive | Baseline to end of study, 24 weeks |
| |||||||||||||||||||||||||||||||||||||
| Primary | Dichotomized Histologic Response (HR): Participant Complete or Partial Response Defined as =/>50% 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 | 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. | All participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug. | Posted | Number | participants | Response assessed at Week 24 ±1 Week |
| ||||||||||||||||||||||||||||||||||||||
| Primary | Dichotomized Clinical Response: Participant Complete or Partial Response Defined as =/>50% 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 | 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. | Analysis includes all participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug. | Posted | Number | participants | Response assessed at Week 24 ±1 Week |
|
Adverse signs and symptoms recorded at each clinic visit beginning week 4 through week 24 (± 1 week). All adverse events followed according to established standards of care. Overall study period: May 2010 to March 2014.
Study source vocabulary for the study began as CTCAE version 3.0 and was translated to version 4.0.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm I (Pioglitazone Hydrochloride) | Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks | 3 | 27 | 22 | 27 | ||
| EG001 | Arm II (Placebo) | Three (3) placebo capsules by mouth once daily for 24 weeks | 1 | 25 | 24 | 25 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| heart failure | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| squamous cell carcinoma of the tongue | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
| |
| laparoscopic hysterectomy | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment | Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy, sacrocolpopexy and midurethral tissue fixation system sling |
|
| Pre-existing abdominal aortic aneurysm | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment | hospitalization for repair of pre-existing abdominal aortic aneurysm |
|
| right femoral artery occlusion | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| palpitations | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| hearing issues | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
| |
| hearing loss, earwax | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
| |
| bilateral burning eye | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| blurred vision | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| conjunctival abrasion | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| conjunctivitis | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| myopia | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| red bloodshot eyes | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| scotoma of right eye | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| vitreous detachment of left eye | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| dry mouth | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| gastritis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| gastrointestinal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| hemorrhoids | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| lump under tongue | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| lip pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| oral dysesthesia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| oral hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| oral pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| periodontal disease | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| rectal hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| striations on tongue | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| red spots right lower lip | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| stomach pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| toothache | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| edema limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| facial pain | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| flu like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| malaise | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| non-cardiac chest pain | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| sluggishness | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| suddenly famished | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| bladder infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| bronchial infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| toe infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| lip infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| sinusitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| skin infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| soft tissue infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| thrush in throat | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| tooth infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| upper respiratory infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| fall | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
| |
| fracture | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
| |
| alanine aminotransferase (ALT) Increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| weight gain | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| weight loss | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| hypoglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| increased chloride | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| arms burning sensaton | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| mild leg cramps at night | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| muscle pain right hip | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| neck pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| rotator cuff trauma resulting from a fall | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| superficial soft tissue fibrosis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| dysgeusia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| hypersomnia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| paresthesia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| sinus pain | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| somnolence | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| tremor | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| insomnia | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| pelvic pain | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
| |
| allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| bronchospasm | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| dry nasal passages | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| productive cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| sinus disorder | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| slight metallic smell | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| tonsillitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| wheezing | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| bee sting | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| skin dyschromia of arms | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| small non-painful reddened area lower left arm | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| keratotic horns on head | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| molar extracted due to failed root canal | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| outpatient surgery, knee meniscus repair | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| trans oral surgery | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| minor venous insufficiency of the legs | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| University of Texas MD Anderson Phase I/II Prevention Consortium | University of Texas (UT) MD Anderson Cancer Center | CR_Study_Registration@mdanderson.org |
| ID | Term |
|---|---|
| D007972 | Leukoplakia, Oral |
| ID | Term |
|---|---|
| D009062 | Mouth Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D007971 | Leukoplakia |
| D011230 | Precancerous Conditions |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077205 | Pioglitazone |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Italy |
|
| Light |
|
| Non-Drinker |
|
| Former |
|
| Never |
|
| OG003 | Placebo: CRP>5 End of Study | Measure at end of Placebo treatment, approximately 24 weeks |
|
|
|
|
|
|
| OG003 | Placebo: End of Study | Measure at end of Placebo treatment, approximately 24 weeks |
|
|
| OG003 | Placebo: End of Study | Measure at end of Placebo treatment, approximately 24 weeks |
|
|
| OG003 | Placebo: End of Study | Measure at end of Placebo treatment, approximately 24 weeks |
|
|
| OG003 | Placebo: End of Study | Measure at end of Placebo treatment, approximately 24 weeks |
|
|
Measure at baseline, followed by Placebo treatment three capsules orally/day for 24 weeks |
| OG003 | Placebo: End of Study | Measure at end of Placebo treatment, approximately 24 weeks |
|
|
Three (3) placebo capsules by mouth once daily for 24 weeks |
|
|
|
|