Head and Neck CancerPhase 2NCT00099021

Pioglitazone Hydrochloride in Preventing Head and Neck Cancer in Patients With Oral Leukoplakia

A Phase 2 study testing pioglitazone hydrochloride in people with Head and Neck Cancer and Oral Leukoplakia, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This phase II trial studies how well pioglitazone hydrochloride works in preventing head and neck cancer in patients who have oral leukoplakia. Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Head and Neck Cancer, Oral Leukoplakia
What is being tested?: pioglitazone hydrochloride
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 21 participants
Where: 1 siteUnited States
Study dates: Jun 2003to 27 Jun 2008
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

Criteria:

ECOG 0-2
Diagnosis of oral cavity or oropharyngeal leukoplakia meeting 1 of the following criteria:
Biopsy-proven hyperplasia in high-risk anatomic areas (e.g., floor of the mouth, mobile tongue, oropharynx, or in any erythroplakia lesion)
Mild, moderate, or severe dysplasia at any site of the oral cavity or oropharynx within the lesion
Measurable lesion that is clinically characterized by leukoplakia, erythroplakia, or erythroleukoplakia
Able to be assessed by bi-directional measurements
Life expectancy: More than 3 months
Hemoglobin >= lower limit of normal for males and post-menopausal females OR
Hemoglobin >= 11 g/dL for premenopausal females
WBC > 3,000/mm^3
Hepatic: Bilirubin < 1.5 times upper limit of normal (ULN); AST and ALT < 1.5 times ULN
Renal: BUN < 1.5 times ULN; Creatinine < 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception
No contraindication to thiazolidinediones
No allergy to pioglitazone or other thiazolidinediones
No serious oral infection
No invasive carcinoma within the past 60 months except nonmelanoma skin cancer or carcinoma in situ of the cervix
No concurrent malignancy
More than 3 months since prior biologic or immunologic therapy
No concurrent insulin for diabetes
No prior radiotherapy to the oral cavity
More than 3 months since prior chemopreventative agents
More than 3 months since prior experimental therapy
More than 3 months since prior megadose vitamins or alternative therapy
No prior thiazolidinediones
No prior participation in this study
No concurrent pharmacologic treatment for diabetes
Concurrent chronic use of non-steroidal anti-inflammatory drugs allowed
Platelet count > 125,000/mm^3
Index lesion must be located in an anatomic site accessible by punch biopsy

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: A Phase IIa Cancer Prevention Trial of the PPAR Gamma Agonist Pioglitazone in Oral Leukoplakia

Read the detailed description

PRIMARY OBJECTIVES:

Determine whether pioglitazone (pioglitazone hydrochloride) reverses leukoplakia in patients with hyperplastic or dysplastic oral cavity or oropharyngeal leukoplakia.

SECONDARY OBJECTIVES:

Determine the safety and tolerability of this drug in these patients.

OUTLINE: This is an open-label study.

Patients receive pioglitazone hydrochloride orally (PO) once daily (QD) for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma.

Patients are followed up at 4, 8, 12, and 16 weeks.

Conditions: Head and Neck Cancer, Oral Leukoplakia
Being tested: pioglitazone hydrochloride
Medical subject headings: Head and Neck Neoplasms, 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
Given PO

Study groups in NCT00099021
Study group	Role	What they receive
Prevention (pioglitazone hydrochloride)	Experimental	Patients receive pioglitazone hydrochloride PO QD for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma. Receives: Drug: pioglitazone hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

Patients' Overall Response
Overall Response= reviewing both the clinical and histological responses and assigning the worst category.
Complete Response (CR) = Clinical CR and Histologic CR, or Histologic CR Partial Response (PR) = Clinical CR or PR and Histologic PR or Stable Disease (SD) Stable Disease (SD) = Clinical SD and Histologic PR or SD Progressive Disease (PD) = Clinical PD and/or Histologic PD
Measured: Week 16 (4 weeks post dose)

Secondary outcomes (2)

Patients' Clinical Response
Determined by measurement of lesions- Complete Response (CR)= disappearance of all lesions, Partial Response (PR)= >or= 50% decrease in sum of lesions, Stable Disease (SD) = does not meet CR,PR or Progressive Disease (PD), and PD= >or= 25% increase in sum of lesions
Measured: Week 16 (4 weeks post dose)
Patients' Histological (Tissue) Response
Determined by biopsy results before and 4 weeks after treatment: Complete Response (CR) =complete reversal of dysplasia or hyperplasia, Partial Response (PR) = >or=50% decrease in sum of lesions, no increase in 1 or more lesions and no new lesion occurs, Stable Disease (SD0 = not CR, PR or Progressive Disease (PD), PD = >or= 25% increase in sum of lesions or new lesion or progression to invasive carcinoma.
Measured: Week 16 (4 weeks post dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 200327 Jun 2008

First posted9 Dec 2004 (estimated)
Study startJun 2003
Primary completion27 Jun 2008
Study completion27 Jun 2008

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 (2)Papers the sponsor has linked to this study.
Other trials for Head and Neck CancerStudies 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: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 21 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00099021
Sponsor's protocol ID: NCI-2009-00862
Other IDs: NCI-2009-00862, CDR0000393562, 2001LS068, 0109 M 07254, N01-CN-15000, N01CN15000
Status last verified: Jan 2022
First submitted: 8 Dec 2004
Last updated: 11 Feb 2022
Results posted: Yes, on ClinicalTrials.gov

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
Puri A, Wuertz B, Rhodus NL, Ondrey FG. Safety of oral mucosal punch biopsy and other oral biospecimen collections in clinical research. Oral Surg Oral Med Oral Pathol Oral Radiol. 2025 Mar;139(3):344-351. doi: 10.1016/j.oooo.2024.10.084. Epub 2024 Oct 30.
PubMed 39532605

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)

All Head and Neck Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase IIa Cancer Prevention Trial of the PPAR Gamma Agonist Pioglitazone in Oral Leukoplakia
ClinicalTrials.gov ID: NCT00099021
Acronym / sponsor ID: NCI-2009-00862
Conditions: Head and Neck Cancer, Oral Leukoplakia
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 21 participants (actual)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: Jun 2003
Primary completion: 27 Jun 2008 (actual)
Study completion: 27 Jun 2008 (actual)
First posted: 9 Dec 2004 (estimated)
Results: Posted 25 Nov 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

Determine whether pioglitazone (pioglitazone hydrochloride) reverses leukoplakia in patients with hyperplastic or dysplastic oral cavity or oropharyngeal leukoplakia.

SECONDARY OBJECTIVES:

Determine the safety and tolerability of this drug in these patients.

OUTLINE: This is an open-label study.

Patients receive pioglitazone hydrochloride orally (PO) once daily (QD) for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma.

Patients are followed up at 4, 8, 12, and 16 weeks.

Study design

Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Prevention (pioglitazone hydrochloride)	Experimental	Drug: pioglitazone hydrochloridePatients receive pioglitazone hydrochloride PO QD for 12 weeks in the absence of disease progression, unacceptable toxicity, or the development of carcinoma.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

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, pioglitazoneGiven PO	Drug	Prevention (pioglitazone hydrochloride)

Primary outcome

Patients' Overall Response
Time frame: Week 16 (4 weeks post dose)
Overall Response= reviewing both the clinical and histological responses and assigning the worst category. Complete Response (CR) = Clinical CR and Histologic CR, or Histologic CR Partial Response (PR) = Clinical CR or PR and Histologic PR or Stable Disease (SD) Stable Disease (SD) = Clinical SD and Histologic PR or SD Progressive Disease (PD) = Clinical PD and/or Histologic PD

2 secondary outcomes

Patients' Clinical Response
Time frame: Week 16 (4 weeks post dose)
Patients' Histological (Tissue) Response
Time frame: Week 16 (4 weeks post dose)

Results and safety

Results posted to the registry on 25 Nov 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pioglitazone Patients	21	21

Primary outcome: Patients' Overall Response

Time frame: Week 16 (4 weeks post dose). Number. Unit: Participants

Measure	Pioglitazone Patients n = 21
Complete Response	0
Partial Response	15
Stable Disease	2
Progressive Disease	4
Partial + Complete Response	15

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of Pioglitazone through Week 16 (end of study).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pioglitazone Patients	0 of 21 (0%)	18 of 21 (85.7%)	Not reported

Limitations and caveats (from the sponsor): Study was closed prior to full accrual because results were very good and funding was discontinued (R-01 application was filed.) Immunohistochemistry (Outcomes #4 through #12) were not done due to laboratory limitations of time.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
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.
Derived from this study: PubMed 39532605Puri A, Wuertz B, Rhodus NL, Ondrey FG. Safety of oral mucosal punch biopsy and other oral biospecimen collections in clinical research. Oral Surg Oral Med Oral Pathol Oral Radiol. 2025 Mar;139(3):344-351. doi: 10.1016/j.oooo.2024.10.084. Epub 2024 Oct 30.

Related trials for Head and Neck Cancer

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)

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.

Frank Ondrey principal investigator

University of Minnesota Medical Center-Fairview

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing pioglitazone hydrochloride in people with Head and Neck Cancer and Oral Leukoplakia, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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: finished, as of the sponsor's last update on 11 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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. 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 25 Nov 2009). 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?

Patients' Overall Response (time frame: Week 16 (4 weeks post dose)). 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 NCT00099021, which also lists 2 linked publications.

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 11 Feb 2022.