Pioglitazone-Metformin Combination Treatment for High Risk Oral Preneoplasia

NCT05727761 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ENT-2022-31139
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (3)

• Clinical change in leukoplakia

  a partial or complete clinical response defined as 50% or greater reduction in the sum of measured targeted lesions

  after 12 weeks of intervention or at early termination.

• histologic change in leukoplakia

  reduction of the leukoplakia grade in \> 50% of treated participants

  after 12 weeks of intervention or at early termination.

• Change in Ki-67

  Ki-67 proliferative indices in lesions

  After 12 weeks of intervention or at early termination

Study Arms (1)

oral leukoplakia patients

EXPERIMENTAL

36 total high risk oral leukoplakia patients.

Drug: pioglitazone-metformin

Interventions

pioglitazone-metformin DRUG

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

oral leukoplakia patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

HealthPartners

Saint Paul, Minnesota, 55130, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 39584361 DERIVED

MeSH Terms

Conditions

Leukoplakia, Oral

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Leukoplakia; Precancerous Conditions; Mouth Diseases; Stomatognathic Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Frank Ondrey

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Beverly Wuertz

CONTACT

612-625-3090; knier003@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Treatment with pioglitazone-metformin (15mg/500mg) twice a day for 12 weeks in 36 total high risk oral leukoplakia patients.

Study Record Dates

• First Submitted: January 19, 2023
• First Posted: February 14, 2023
• Study Start: January 1, 2025
• Primary Completion (Estimated): July 28, 2026
• Study Completion (Estimated): July 28, 2026
• Last Updated: December 24, 2025

Record last verified: 2025-12

Locations

US (2)