Pioglitazone-Metformin Combination Treatment for High Risk Oral Preneoplasia

NCT ID: NCT05727761

Last Updated: 2025-12-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-01
• Study Completion Date: 2026-07-28

Brief Summary

This is a Phase IIa oral cavity leukoplakia study of pioglitazone 15mg and metformin 500mg BID for 12 weeks. The primary objective is to determine the clinical and histologic changes of leukoplakia from baseline following a 12 week course of twice daily pioglitazone-metformin. Outcomes are defined as are a reduction of the leukoplakia grade in > 50% of treated participants and a partial or complete clinical response defined as 50% or greater reduction in the sum of measured targeted lesions. In addition, participants who show clinical and histologic improvement should correlate with a significant reduction of Ki-67 proliferative indices in lesions of these participants as compared to baseline.

Conditions

Oral Leukoplakia

Keywords

oral leukoplakia; oral cancer prevention; pioglitazone; metformin; precancerous oral lesion

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

oral leukoplakia patients

36 total high risk oral leukoplakia patients.

Group Type: EXPERIMENTAL

pioglitazone-metformin

Intervention Type: DRUG

Treatment with pioglitazone-metformin (15mg/500mg) twice a day for 12 weeks

Interventions

pioglitazone-metformin

Treatment with pioglitazone-metformin (15mg/500mg) twice a day for 12 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Biopsy proven hyperplasia in high risk anatomic areas (floor of mouth, mobile tongue, oropharynx). Hyperplasia or dysplasia of any grade in any erythroplakia lesion. Mild, moderate or severe dysplasia within the lesion at any site of the oral cavity or oropharynx.
• Must have objective evidence of oral leukoplakia that is measurable in 2 dimensions per RECIST. The lesion(s) may be clinically characterized by leukoplakia, erythroplakia, erythro/leukoplakia. Lesions may be located in the oral cavity or oropharynx. However, the index lesion must be located in an anatomic site accessible by punch biopsy and be a minimum of 4mm x 8 mm to permit a 4mm punch biopsy.
• Age 18 years or older at the time of consent.
• Evidence of adequate organ function within 14 days prior to Day 1
• Able to comply with treatment (i.e. able to swallow a tablet whole, not crushed) and complete a 12 week course of twice daily medication as required by this study in the opinion of the treating investigator.
• Body mass index (BMI) is ≥ 18.5.
• Sexually active persons of child-bearing potential agrees to use adequate contraception (a hormonal method that has been in continual use for a minimum of 3 months prior to the study screening visit, a barrier method, or abstinence) for the duration of study participation.
• Provides voluntary written consent prior to the performance of any research related activity.

Exclusion Criteria

• Pregnant or breastfeeding or planning to become pregnant.
• A concurrent diagnosis of Type I or Type II diabetes that is being treated with insulin or an antidiabetic agent. Participants whose Type II diabetes is controlled with diet and/or exercise alone are eligible provided they meet all other eligibility criteria.
• Participant is taking another investigational agent (not approved by the FDA for any indication).
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ACTOplus Met, pioglitazone or metformin.
• Any contraindication to biopsy - this study requires a 4 mm punch biopsy of a lesion and of nearby normal tissue prior to treatment and at the end of the 12 week treatment period.
• History of bladder cancer, including in situ bladder cancer.
• History of invasive cancer (other than non-melanoma skin cancer or cervical cancer in situ) active within 18 months prior to the baseline study visit. (Participants who have a history of cancer that was curatively treated without evidence of recurrence in the 18 months prior to the baseline study visit are considered eligible).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank Ondrey

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

HealthPartners

Saint Paul, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Beverly Wuertz

Role: CONTACT

Phone: 612-625-3090

Email: knier003@umn.edu

Facility Contacts

Beverly Wuertz

Role: primary

Kirsten Dalrymple

Role: primary

References

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.

Reference Type: DERIVED

PMID: 39584361 (View on PubMed)

Other Identifiers

ENT-2022-31139

Identifier Type: -

Identifier Source: org_study_id