NCT05237960

Metformin for the Prevention of Oral Cancer in Patients With Oral Leukoplakia or Erythroplakia

M4OC-Prevent 2.0: Phase IIb Trial of Metformin for Oral Cancer Prevention

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: University of Arizona · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

This phase IIb trial tests whether metformin works in preventing oral cancer in patients with oral leukoplakia (white patches) or erythroplakia (red patches). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in the blood. It decreases the amount of glucose patients absorb from food and the amount of glucose made by the liver. Metformin also increases the body's response to insulin, a natural substance that controls the amount of glucose in the blood. This trial may help researchers determine if metformin can stop changes in the mouth that are related to pre-cancer growths in the mouth.

Detailed description

PRIMARY OBJECTIVE: I. To determine the histological response to metformin hydrochloride (metformin) intervention in the target lesion. SECONDARY OBJECTIVES: I. Clinical response to metformin intervention in the target lesion. II. Effect of metformin on cell proliferation (Ki67) and its molecular targets (pS6 and nuclear YAP) in the target lesion. III. Metformin effect on serum metabolic markers (C-peptide, glucose and HbA1c). IV. Trough plasma metformin concentrations. EXPLORATORY OBJECTIVES: I. Expression of dysregulated molecular mechanisms in the target lesion, including, in order of priority, p53, PTEN, p16, EGFR, and pEGFR. II. Immune cell infiltration and markers of inflammation in the target lesion. III. Analysis of genomic alterations in the target lesion and blood deoxyribonucleic acid (DNA). IV. Microbiome in oral rinses. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive extended release metformin hydrochloride orally (PO) once daily (QD) for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and biopsy at baseline and week 24. ARM II: Patients receive a placebo PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and biopsy at baseline and week 24. After completion of study treatment, patients are followed for up to 3 weeks.

Conditions

• Erythroplakia
• Oral Leukoplakia

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo biopsy
PROCEDURE	Biospecimen Collection	Correlative studies
DRUG	Extended Release Metformin Hydrochloride	Given PO
DRUG	Placebo Administration	Given PO

Timeline

• Start date: 2023-01-12
• Primary completion: 2025-12-31
• Completion: 2026-12-01
• First posted: 2022-02-14
• Last updated: 2025-09-29

Locations

10 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study