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

Metformin Chemoprevention of Oral Premalignant Lesions

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.

Study Overview

• Status: Terminated
• Conditions: Oral Cavity Carcinoma; Leukoplakia; Erythroplakia; Proliferative Verrucous Leukoplakia
• Intervention / Treatment: Procedure: Biopsy; Drug: Metformin

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the transformation-free-survival in lesion types erythroplakia (EP) and verrucous hyperplasia (VH). 'Transformation' is defined as the development of invasive cancer.

SECONDARY OBJECTIVE:

I. To evaluate the current spontaneous regression rates, i.e., percentages of patients having lesion disappear within 1-year post treatment, in all four lesion types and compare them with historical documented regression rate in literature.

EXPLORATORY OBJECTIVE:

I. To evaluate the transformation-free-survival in lesion types homogenous leukoplakia (HL) and non-homogenous leukoplakia (NHL).

OUTLINE:

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

After completion of study treatment, patients are followed up every 3 months for 24 months.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Laboratory results

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prevention (metformin); Patients receive metformin PO QD on days 1-3 and then PO BID for up to 12 months in the absence of unacceptable toxicity.	Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Drug: Metformin; Given PO; Other Names: 1-Dimethylbiguanide; 657-24-9; N-dimethylbiguanide; N-Dimethylimidodicarbonimidic Diamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lesion status	Evaluated on a Likert-scale with three levels: 'worsen', 'same' and 'disappear', compared to each patient's baseline lesion status (as measured at pre-treatment and one year post initiation of treatment). The lesion size and status evaluated at 1-year post-treatment will be summarized using percentages as well as 95% Clopper-Pearson exact confidence intervals. The current spontaneous regression rates (i.e., percentage of 'disappear') will be compared against the historically documented regression rate of 35% using two-sided exact binomial test.	Baseline to 1 year after treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transformation-free-survival, in lesion types homogenous leukoplakia and non-homogenous leukoplakia	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

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2022
• Primary Completion (Actual): March 16, 2024
• Study Completion (Actual): March 16, 2024

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 7, 2022
• First Posted (Actual): September 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Pathological Conditions, Anatomical; Precancerous Conditions; Leukoplakia; Erythroplasia; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 22D.296

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No