A Phase 2 interventional study of Pioglitazone hydrochloride and placebo in Oral Leukoplakia, sponsored by National Cancer Institute (NCI). Terminated at 13 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-04-06.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
Among 20 studies in Leukoplakia, Oral with a site in United States — 1 open to participants now, 3 under way, none of them phase 3. Leukoplakia, Oral · United States.
Among the 20 studies in Leukoplakia, Oral with a site in United States, this one is the 3rd largest by enrollment of the 15 interventional ones that give a count, is the only one that started in 2010, is one of 11 in phase 2, and was the 12th registered.
48 studies on the registry are indexed under Leukoplakia, Oral; 11 are open to participants now.
Browse Leukoplakia, Oral studies →1 of the 20 studies in Leukoplakia, Oral with a site in United States is open now. Recruiting first, the newest first:
University of Minnesota · Sites in United States
Ages 18+
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 7 Leukoplakia, Oral studies recruiting now, 5 set no upper age limit and none stop at 75 or younger; none take children under 18; 1 takes healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
20 studies; the count open now beside each. This study's row is marked.
First in 1996; this study’s year is marked. 1 started in 2010.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 52 is above the median of 36 across 23 interventional studies indexed under Leukoplakia, Oral.
Median enrollment 26 across the 15 interventional studies, 487 across the 2 observational. Of the 15 that completed or were terminated, 6 (40%) have results posted.
This tab as a report to print or save as PDF → With an account.
4 of 20 have an industry lead sponsor. The 10 most frequent:
National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 412 completed or terminated interventional studies of FDA-regulated products, 374 (91%) have results posted.
National Cancer Institute (NCI) has 7 studies filed under Leukoplakia, Oral — fewer than ten, so there is no comparison to draw.
1 of the studies in Leukoplakia, Oral with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT05727761University of MinnesotaPioglitazone-Metformin Combination Treatment for High Risk Oral Preneoplasia | 2027-07-30 |
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Among the 20 studies in Leukoplakia, Oral with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Males or females with a suspected or 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 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:
Hyperplastic leukoplakia of a high-risk site
An ADVANCED premalignant lesion defined as the presence of at least one of the following:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks
Drug: Pioglitazone hydrochloride · Other: laboratory biomarker analysis
Three (3) placebo capsules by mouth once daily for 24 weeks
Other: placebo · Other: laboratory biomarker analysis
Three (3) pioglitazone 15 mg capsules by mouth once daily for 24 weeks (+/- 1 week)
Also known as: Actos, pioglitazone
Three (3) pioglitazone placebo capsules by mouth once daily for 24 weeks (+/- 1 week)
Also known as: PLCB
Correlative studies
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.
Time frame: 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.
Time frame: 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.
Time frame: Response assessed at Week 24 ±1 Week
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.
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
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.
Time frame: 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.
Time frame: 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.
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)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline to end of study, 24 weeks
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.
| Milestone | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Started | 27 | 25 |
| Completed | 21 | 23 |
| Not completed | 6 | 2 |
| Withdrew: Adverse event | 4 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 |
| Withdrew: Noncompliance | 1 | 0 |
| Withdrew: Disease progression | 0 | 1 |
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.
| participants | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Response | 12 | 8 |
| No Response | 14 | 17 |
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.
| participants | Pioglitazone: CRP>5 at Baseline | Pioglitazone: CRP>5 End of Study | Placebo: CRP> 5 Baseline | Placebo: CRP>5 End of Study |
|---|---|---|---|---|
| Yes | 6 | 1 | 4 | 4 |
| No | 18 | 19 | 21 | 17 |
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.
| participants | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Yes | 3 | 0 |
| No | 15 | 21 |
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.
| participants | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Never Smoked | 4 | 5 |
| Former Smoker | 5 | 2 |
| Current Smoker | 2 | 1 |
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.
| participants | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Non-Drinker | 2 | 2 |
| Light Drinker | 8 | 6 |
| Heavy Drinker | 1 | 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.
| participants | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Blood & Lymphatic System Disorders | 1 | 0 |
| Cardiac Disorders | 3 | 2 |
| Ear & Labyrinth Disorders | 0 | 2 |
| Eye Disorders | 7 | 2 |
| Gastrointestinal Disorders | 23 | 22 |
| General Disorders & Administration Site Conditions | 12 | 10 |
| Infections and Infestations | 9 | 8 |
| Injury, Poisoning and Procedural Complications | 0 | 2 |
| Investigations | 3 | 2 |
| Metabolism and Nutrition Disorders | 2 | 0 |
| Musculoskeletal and Connective Tissue Disorders | 7 | 8 |
| Neoplasms Benign, Malignant and Unspecified | 1 | 0 |
| Nervous System Disorders | 14 | 7 |
| Psychiatric Disorders | 3 | 1 |
| Reproductive System and Breast Disorders | 1 | 0 |
| Respiratory, Thoracic and Mediastinal Disorders | 18 | 9 |
| Skin and Subcutaneous Tissue Disorders | 4 | 2 |
| Surgical and Medical Procedures | 2 | 3 |
| Vascular Disorders | 5 | 12 |
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.
| percentage of staining cells positive | Pioglitazone: Baseline | Pioglitazone: End of Study | Placebo: Baseline | Placebo: End of Study |
|---|---|---|---|---|
| Biomarker Measurements at Scheduled Visits: Tissue Levels of Cyclin D1 | 15.5 ± 10.0 | 12.7 ± 6.9 | 12.8 ± 7.9 | 12.9 ± 7.0 |
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.
| percentage of staining cells positive | Pioglitazone: Baseline | Pioglitazone: End of Study | Placebo: Baseline | Placebo: End of Study |
|---|---|---|---|---|
| Biomarker Measurements at Scheduled Visits: Tissue Levels of Ki-67 | 9.2 ± 4.6 | 8.9 ± 4.2 | 10.7 ± 6.5 | 8.2 ± 4.6 |
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.
| percentage of staining cells positive | Pioglitazone: Baseline | Pioglitazone: End of Study | Placebo: Baseline | Placebo: End of Study |
|---|---|---|---|---|
| Biomarker Measurements at Scheduled Visits: Tissue Levels of p21 | 18.7 ± 10.2 | 19.3 ± 10.6 | 17.7 ± 10.8 | 15.6 ± 7.4 |
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.
| percentage of staining cells positive | Pioglitazone: Baseline | Pioglitazone: End of Study | Placebo: Baseline | Placebo: End of Study |
|---|---|---|---|---|
| Biomarker Measurements at Scheduled Visits: Tissue Levels of B-cell Lymphoma 2 (Bcl2) | 2.8 ± 3.2 | 2.3 ± 2.3 | 4.2 ± 5.0 | 4.6 ± 8.3 |
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.
| percentage of staining cells positive | Pioglitazone: Baseline | Pioglitazone: End of Study | Placebo: Baseline | Placebo: End of Study |
|---|---|---|---|---|
| PPARG Nucleus | 10.8 ± 15.7 | 7.3 ± 7.5 | 12.4 ± 10.4 | 6.8 ± 7.2 |
| PPARG Cytoplasm | 21.7 ± 25.8 | 23.5 ± 28.0 | 20.2 ± 29.9 | 21.5 ± 31.3 |
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.
| participants | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Response | 2 | 2 |
| No Response | 24 | 23 |
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.
| participants | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Response | 11 | 8 |
| No Response | 15 | 17 |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I (Pioglitazone Hydrochloride) | — | 3/27 (11.1%) | 22/27 (81.5%) |
| Arm II (Placebo) | — | 1/25 (4%) | 24/25 (96%) |
| Event | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| Pre-existing abdominal aortic aneurysmSurgical and medical procedures | 0/27 | 1/25 |
| right femoral artery occlusionVascular disorders | 0/27 | 1/25 |
| heart failureCardiac disorders | 1/27 | 0/25 |
| sepsisInfections and infestations | 1/27 | 0/25 |
| squamous cell carcinoma of the tongueNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/27 | 0/25 |
| laparoscopic hysterectomySurgical and medical procedures | 1/27 | 0/25 |
| Event | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) |
|---|---|---|
| hypertensionVascular disorders | 4/27 | 11/25 |
| oral painGastrointestinal disorders | 6/27 | 4/25 |
| headacheNervous system disorders | 5/27 | 2/25 |
| fatigueGeneral disorders | 3/27 | 4/25 |
| coughRespiratory, thoracic and mediastinal disorders | 3/27 | 4/25 |
| sore throatRespiratory, thoracic and mediastinal disorders | 4/27 | 1/25 |
| nauseaGastrointestinal disorders | 2/27 | 3/25 |
| dry mouthGastrointestinal disorders | 3/27 | 1/25 |
| vomitingGastrointestinal disorders | 3/27 | 1/25 |
| dizzinessNervous system disorders | 3/27 | 2/25 |
| Age, Continuous(years) | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| Mean | 59.9 ± 8.3 | 59.0 ± 10.3 | 59.5 ± 9.2 |
| Sex: Female, Male(Participants) | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| Female | 16 | 12 | 28 |
| Male | 11 | 13 | 24 |
| Ethnicity (NIH/OMB)(Participants) | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| Hispanic or Latino | 2 | 1 | 3 |
| Not Hispanic or Latino | 25 | 24 | 49 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 2 | 1 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 25 | 24 | 49 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| United States | 23 | 22 | 45 |
| Italy | 4 | 3 | 7 |
| Alcohol Use at Baseline(participants) | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| Heavy | 2 | 3 | 5 |
| Light | 17 | 17 | 34 |
| Non-Drinker | 8 | 5 | 13 |
| Smoking Use at Baseline(participants) | Arm I (Pioglitazone Hydrochloride) | Arm II (Placebo) | Total |
|---|---|---|---|
| Current | 6 | 6 | 12 |
| Former | 12 | 7 | 19 |
| Never | 9 | 12 | 21 |
The record gives a start of Feb 2010, a primary completion of Mar 2014 and a completion of Mar 2014. It does not say whether these dates are actual or estimated.
Results were first posted in Apr 2016, 2 years 1 month after primary completion.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Pioglitazone
National Cancer Institute (NCI) →