Oral LeukoplakiaPhase 2NCT00951379
Pioglitazone for Oral Premalignant Lesions
A Phase 2 study testing Pioglitazone hydrochloride and laboratory biomarker analysis in people with Oral Leukoplakia, run by National Cancer Institute (NCI) at 13 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oral Leukoplakia
- What is being tested?
- Pioglitazone hydrochloride and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 13 sitesin 3 countries
- Study dates
- Feb 2010to Mar 2014
- 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
- 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
- If a participant has had a biopsy of the target oral premalignant lesions (OPL) lesion(s) within 6 weeks prior to the screening visit and archival tissue is available and the participant agrees to have archival tissue used for histologic confirmation and biomarker analysis, then NO additional biopsies (of the OPL) need to be performed at the screening visit; the pre-screening biopsy must undergo centralized pathology review before the second stage of registration can be performed; if archival tissue is not available, a waiting period of 6 weeks from the time of the last biopsy must be observed before re-biopsy for study purposes
- If a participant has not had a biopsy of the suspected OPL at the time of the screening visit, then a biopsy of the lesion must be performed during the screening visit; the screening biopsy must undergo centralized pathology review before the second stage of registration can be performed
- 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
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- 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
- Dorsal, lateral or ventral tongue
- Floor of mouth
- An ADVANCED premalignant lesion defined as the presence of at least one of the following:
- Moderate dysplasia
- Severe dysplasia (excluding carcinoma in situ)
- Erythroplakia (due to the high risk for progression associated with erythroplakia, erythroplakia of any histology will be defined as an ADVANCED oral premalignant lesion)
- 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
Who cannot join
- The participant has active cancer or carcinoma in situ of the head and neck
- The participant has a contraindication to biopsy
- The participant has presence of congestive heart failure (New York Heart Association (NYHA) class II-IV), uncontrolled hypertension (systolic > 150 or diastolic > 100), or unstable angina
- The participant has any history of congestive heart failure or history of myocardial infarction within the past 6 months
- The participant exhibits clinical evidence of active liver disease or history of chronic liver disease
- The participant has > Common Terminology Criteria for Adverse Events (CTCAE) grade 1 edema
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- The participant has known diabetes and is on insulin or oral agents; the participant is receiving medical therapy for dysregulated blood sugar
- The participant who currently receives an enzyme inhibitor of CYP2C8 (gemfibrozil, ketoconazole, quercetin, trimethoprim), or enzyme inducer of CYP2C8 (cortisol, dexamethasone, phenobarbital, rifampin), or CYP3A4 substrate will not be eligible for randomization after assessing eligibility in stage two unless he/she will not be eligible for randomization after assessing eligibility in stage two unless he/she is willing to stop these drugs and possibly replace them with alternative therapies
- The participant currently receives pregabalin or thioridazine
- The participant has experienced jaundice with Rezulin (troglitazone)
- The participant has a history of colorectal cancer, familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (HNPCC)
- The participant has a history of bladder cancer or in situ bladder cancer
- The participant has a history of invasive cancer within the past 18 months (excluding non-melanoma skin cancer and in situ cervical cancer); participants (excluding those with a history of colorectal cancer, FAP, HNPCC, bladder cancer or in situ bladder cancer) who received curative treatment and have shown no evidence of recurrence for 18 months will be eligible
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
United States11 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263
Medical University of South Carolina
Charleston, South Carolina, 29425
MD Anderson Cancer Center
Houston, Texas, 77030
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
Columbia University Medical Center
New York, New York, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Weill Medical College of Cornell University
New York, New York, 10065
Canada1 site
BC Cancer Agency (Vancouver Cancer Centre)
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: Phase IIB Randomized, Placebo Controlled Trial of Pioglitazone for Oral Premalignant Lesions an Inter-consortium Collaborative Study
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Oral Leukoplakia
- Being tested
- Pioglitazone hydrochloride, placebo, laboratory biomarker analysis
- Medical subject headings
- Leukoplakia, Oral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone hydrochlorideDrug
Also called Actos, pioglitazone
Three (3) pioglitazone 15 mg capsules by mouth once daily for 24 weeks (+/- 1 week)
placeboOther
Also called PLCB
Three (3) pioglitazone placebo capsules by mouth once daily for 24 weeks (+/- 1 week)
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Pioglitazone Hydrochloride) | Experimental | Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks Receives: Drug: Pioglitazone hydrochloride; Other: laboratory biomarker analysis |
| Arm II (Placebo) | Placebo comparator | Three (3) placebo capsules by mouth once daily for 24 weeks Receives: Other: placebo; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Response assessed at Week 24 ±1 Week
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.
Measured: Response assessed at Week 24 ±1 Week
Secondary outcomes (10)
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.
Measured: Baseline to end of study, 24 weeks
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to end of study, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2009 (estimated)
- Study startFeb 2010
- Primary completionMar 2014
- Study completionMar 2014
Why it stopped: Due to slow accrual.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Oral LeukoplakiaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Powel H. Brown, Principal investigator, University of Texas MD Anderson Cancer Center, Consortium PI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00951379
- Sponsor's protocol ID
- NCI-2012-03152
- Other IDs
- NCI-2012-03152, UWI H-2009-0106, MDA-2009-0339, INC07-10-01, N01CN35159, N01CN35153, P30CA016672
- Status last verified
- Jun 2014
- First submitted
- 31 Jul 2009
- Last updated
- 6 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 39584361
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIB Randomized, Placebo Controlled Trial of Pioglitazone for Oral Premalignant Lesions an Inter-consortium Collaborative Study
- ClinicalTrials.gov ID
- NCT00951379
- Acronym / sponsor ID
- NCI-2012-03152
- Conditions
- Oral Leukoplakia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to slow accrual.
- Enrolment
- 52 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2010
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 4 Aug 2009 (estimated)
- Results
- Posted 6 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (Pioglitazone Hydrochloride) | Experimental | Drug: Pioglitazone hydrochloride, Other: laboratory biomarker analysisThree (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks |
| Arm II (Placebo) | Placebo comparator | Other: placebo, Other: laboratory biomarker analysisThree (3) placebo capsules by mouth once daily for 24 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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
Key exclusion criteria (13 listed)
- The participant has active cancer or carcinoma in situ of the head and neck
- The participant has a contraindication to biopsy
- The participant has presence of congestive heart failure (New York Heart Association (NYHA) class II-IV), uncontrolled hypertension (systolic > 150 or diastolic > 100), or unstable angina
- The participant has any history of congestive heart failure or history of myocardial infarction within the past 6 months
- The participant exhibits clinical evidence of active liver disease or history of chronic liver disease
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 |
|---|---|---|
| Pioglitazone hydrochlorideAlso: Actos, pioglitazoneThree (3) pioglitazone 15 mg capsules by mouth once daily for 24 weeks (+/- 1 week) | Drug | Arm I (Pioglitazone Hydrochloride) |
| placeboAlso: PLCBThree (3) pioglitazone placebo capsules by mouth once daily for 24 weeks (+/- 1 week) | Other | Arm II (Placebo) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (Pioglitazone Hydrochloride), Arm II (Placebo) |
Primary outcome
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>
Time frame: Response assessed at Week 24 ±1 Week
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.
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
Time frame: Response assessed at Week 24 ±1 Week
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.
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
Time frame: Response assessed at Week 24 ±1 Week
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.
10 secondary outcomes
Number of Participants With >5.0 mg/L in Level of C-reactive Protein in Plasma
Time frame: Baseline to end of study, 24 weeks
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
Time frame: Baseline to end of study, 24 weeks
Number of Participant With Clinical Response by Baseline Characteristics: Tobacco Use
Time frame: Up to 26 weeks
Number of Participant With Clinical Response by Baseline Characteristics: Alcohol Use
Time frame: 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)
Time frame: Up to 26 weeks
Biomarker Measurements at Scheduled Visits: Tissue Levels of Cyclin D1
Time frame: Baseline to end of study, 24 weeks
Biomarker Measurements at Scheduled Visits: Tissue Levels of Ki-67
Time frame: Baseline to end of study, 24 weeks
Biomarker Measurements at Scheduled Visits: Tissue Levels of p21
Time frame: Baseline to end of study, 24 weeks
Biomarker Measurements at Scheduled Visits: Tissue Levels of B-cell Lymphoma 2 (Bcl2)
Time frame: Baseline to end of study, 24 weeks
Biomarker Measurements at Scheduled Visits: Tissue Levels of PPARG Nucleus and PPARG Cytoplasm
Time frame: Baseline to end of study, 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39584361Gates 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.
- University of Texas MD Anderson Cancer Center Official WebsiteLink provided by the sponsor.
- National Cancer Institute (NCI) Central Website for Cancer ResearchLink provided by the sponsor.
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Erythroplakia, Fanconi Anemia
RecruitingPhase 2
Pembrolizumab in Treating Participants With Leukoplakia
Erythroleukoplakia, Leukoplakia
RecruitingPhase 2
Pioglitazone-Metformin Combination Treatment for High Risk Oral Preneoplasia
Oral Leukoplakia
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.
Powel H. Brown principal investigator
University of Texas MD Anderson Cancer Center, Consortium PI
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone hydrochloride and laboratory biomarker analysis in people with Oral Leukoplakia, run by National Cancer Institute (NCI) at 13 sites in 3 countries.
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 30 inclusion and 13 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 6 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Canada, Italy. 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. Some participants in this study may receive a placebo. 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 Apr 2016). 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?
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> (time frame: Response assessed at Week 24 ±1 Week). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00951379, which also lists 1 linked publication.
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 6 Apr 2016.