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

NCT05237960 | Active Not Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: NCI-2022-00596Pending12UAZ21-07-01P30CA023074UG1CA242596
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 10

Brief 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.

Conditions

Erythroplakia; Oral Leukoplakia

Outcome Measures

Primary Outcomes (1)

• Histologic response to metformin

  Histologic response will be evaluated by the following criteria: complete response (CR): Complete reversal of dysplasia or hyperplasia to normal epithelium in the target lesion. Partial response (PR): Improvement of the degree of dysplasia or hyperplasia in the target lesion. No change (NC): No change in the degree of dysplasia or hyperplasia in the target lesion, anything that is not CR, PR or PD. Progressive disease (PD): Increase in the severity of grade of histology in the target lesion.

  Up to 24 weeks

Secondary Outcomes (4)

• Clinical response to metformin

  Up to 24 weeks

• Cell proliferation

  Up to 24 weeks

• Serum metabolic markers

  Up to 24 weeks

• Plasma metformin concentrations

  From baseline, up to 24 weeks

Study Arms (2)

Arm I (extended release metformin)

EXPERIMENTAL

Patients receive extended release metformin hydrochloride PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients will also undergo biopsies and blood collections on study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Extended Release Metformin Hydrochloride

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive a placebo PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients will also undergo biopsies and blood collections on study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Drug: Placebo Administration

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Arm I (extended release metformin); Arm II (placebo)

Biospecimen Collection PROCEDURE

Correlative studies

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (extended release metformin); Arm II (placebo)

Extended Release Metformin Hydrochloride DRUG

Given PO

Also known as: ER Metformin Hydrochloride, Extended-release Metformin Hydrochloride, Glucophage XR, Glumetza, Metformin Hydrochloride Extended Release

Arm I (extended release metformin)

Placebo Administration DRUG

Given PO

Arm II (placebo)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with oral leukoplakia or erythroplakia with mild, moderate, or severe histologic dysplasia or hyperplasia at the high risk sites (e.g., floor of mouth, tongue). Lesions arising from the radiation field are excluded as study lesions.
• Measurable disease - minimum lesion size of 8x3 mm before initial biopsy
• Age \>= 21 years. Adults 18-20 are not included as Canadian law prohibits purchase of cigarettes under the age of 21; investigators wish to keep criteria consistent among all trial sites. Also, smokers aged \< 20 years would most likely not have oral leukoplakia
• Current and former smokers (\>= 5 packs in the lifetime)
• Karnofsky performance scale \>= 70%
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count \>= 1,000/microliter
• Platelets \>= 100,000/microliter
• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional ULN
• Estimation glomerular filtration rate (eGFR) \> 45 mL/min (eGFR calculated using the equation Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] creatinine)
• Willing to use adequate contraception (barrier method, abstinence, subject or partner has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation because the effects of metformin on the developing human fetus are unknown even though it is not teratogenic in rats and rabbits at 2-6 times the maximum recommended human daily dose. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

You may not qualify if:

• Patients with diabetes who are being treated with insulin or an anti-diabetic medication
• History of diabetic ketoacidosis
• Participants may not be receiving any other investigational agents within past 3 months at screening
• History of allergic reactions attributed to compounds of similar chemical composition to metformin or prior use of metformin within the last year
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, human immunodeficiency virus (HIV) positive, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Oral carcinoma in situ from the baseline biopsy
• History of chronic alcohol use or abuse defined as any one of the following: a) average consumption of 3 or more alcohol containing beverages daily in the past 12 months; b) consumption of 7 or more alcoholic beverages within a 24 hour (hr) period in the past 12 months
• Hemoglobin A1c (HbA1c) \> 8%
• Pregnancy or nursing women. Pregnant women are excluded from this study because the effects of metformin on the developing human fetus are unknown even though it is not teratogenic in rats and rabbits at 2-6 times the maximum recommended human daily dose. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with metformin, breastfeeding should be discontinued
• Acute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension
• History of renal disease
• Have received hormone therapy, chemotherapy, immunotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) within the past 18 months. History of prior curatively treated cancer, including oral cancer, is allowed as long as all primary and adjuvant treatment is completed \>= 18 months prior to enrollment. Ongoing adjuvant hormonal treatment (e.g., for breast cancer) is allowed.
• Current use of carbonic anhydrase inhibitors (e.g. topiramate, zonisamide, acetazolamide, or dichlorphenamide) or ranolazine

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

Location

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Louisiana State University

Lafayette, Louisiana, 70503, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

NYU College of Dentistry

New York, New York, 10010, United States

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Dalhousie University

Halifax, Nova Scotia, B3H 4R2, Canada

Location

MeSH Terms

Conditions

Erythroplasia; Leukoplakia, Oral

Interventions

Biopsy; Specimen Handling; Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Scott M Lippman

  University of California, San Diego Moores Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: February 14, 2022
• Study Start: January 12, 2023
• Primary Completion: November 7, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (8); CA (2)