Metformin for the Prevention of Oral Cancer in Patients With Oral Premalignant Lesions

NCT05536037 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 22D.296JT 17064
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests whether metformin works in reducing the annual transformation (development of invasive cancer) of oral precancerous lesions into cancerous lesions. Metformin is a drug approved for the treatment of diabetes, but studies have shown that it may have some anticancer properties. Giving metformin may help prevent or slow the development of oral cancer from precancerous lesions.

Conditions

Erythroplakia; Leukoplakia; Oral Cavity Carcinoma; Proliferative Verrucous Leukoplakia

Outcome Measures

Primary Outcomes (1)

• Transformation-free-survival, in lesion types erythroplakia and verrucous hyperplasia

  Will be summarized using Kaplan-Meier curves as well as 95% confidence ands. Kaplan-Meier estimates of the 3-year transformation-free-survival rates will be reported with 95% confidence interval. One-sample two-sided log-rank test will be applied to all four lesions as well.

  Up to 3 years

Secondary Outcomes (1)

• Change in lesion status

  Baseline to 1 year after treatment

Other Outcomes (1)

• Transformation-free-survival, in lesion types homogenous leukoplakia and non-homogenous leukoplakia

  Up to 3 years

Study Arms (1)

Prevention (metformin)

EXPERIMENTAL

Patients receive metformin PO QD on days 1-3 and then PO BID for up to 12 months in the absence of unacceptable toxicity.

Drug: Metformin; Procedure: Biopsy

Interventions

Metformin DRUG

Given PO

Also known as: 1-Dimethylbiguanide, 657-24-9, N-dimethylbiguanide, N-Dimethylimidodicarbonimidic Diamide

Prevention (metformin)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Prevention (metformin)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-85
• Clinical appearance of lesion
• Homogenous leukoplakia
• Non- homogenous leukoplakia
• Erythroplakia
• Proliferative verrucous leukoplakia
• Histologic appearance
• No dysplasia
• Mild dysplasia
• Moderate dysplasia
• Severe dysplasia
• Diabetics: if on metformin, will get them to 2000 mg per day, if not, will add metformin in consultation with endocrinologist
• All subjects must be able to comprehend and sign a written informed consent document
• Willing and able to be available for the duration of the study
• In general good health with no contraindication to biopsy or metformin therapy

You may not qualify if:

• Carcinoma in-situ, verrucous carcinoma, invasive squamous cell carcinoma (SCCa)
• Exclude systemic causes of the lesion: pemphigus, pemphigoid, systemic lupus erythematosus (SLE), lichenoid drug reaction, human immunodeficiency virus (HIV), syphilis
• Exclude local inciting factors: rule out (r/o) but allowing 2 weeks to pass and see if there is resolution, if not and doesn't resolve with local measures, medical treatment, enroll
• Frictional: sharp tooth
• Trauma
• Immunosuppression by natural illness or medically induced
• Hypersensitivity or allergic reaction to metformin or some other contraindication

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Erythroplasia; Leukoplakia; Mouth Neoplasms

Interventions

Metformin; Biopsy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: September 10, 2022
• Study Start: May 4, 2022
• Primary Completion: March 16, 2024
• Study Completion: March 16, 2024
• Last Updated: May 15, 2025

Record last verified: 2025-05

Locations

US (1)