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

Primary Purpose

Erythroplakia, Leukoplakia, Oral Cavity Carcinoma

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Metformin

Biopsy

About this trial

This is an interventional prevention trial for Erythroplakia

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Thomas Jefferson University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Prevention (metformin)

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT05536037

First Posted

September 7, 2022

Last Updated

December 13, 2022

Sponsor

Thomas Jefferson University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT05536037

Brief Title

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

Official Title

Metformin Chemoprevention of Oral Premalignant Lesions

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 4, 2022 (Actual)

Primary Completion Date

March 2024 (Anticipated)

Study Completion Date

March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Thomas Jefferson University

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Erythroplakia, Leukoplakia, Oral Cavity Carcinoma, Proliferative Verrucous Leukoplakia

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

116 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Prevention (metformin)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

1-Dimethylbiguanide, 657-24-9, N-dimethylbiguanide, N-Dimethylimidodicarbonimidic Diamide

Intervention Description

Given PO

Intervention Type

Procedure

Intervention Name(s)

Biopsy

Other Intervention Name(s)

BIOPSY_TYPE, Bx

Intervention Description

Undergo biopsy

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to 3 years

Secondary Outcome Measure Information:

Title

Change in lesion status

Description

Time Frame

Baseline to 1 year after treatment

Other Pre-specified Outcome Measures:

Title

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

Description

Time Frame

Up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Andrew Yampolsky, DDS, MD

Phone

215-955-6215

Andrew.Yampolsky@jefferson.edu

First Name & Middle Initial & Last Name or Official Title & Degree

James Gates, DMD, MD

Phone

215-955-6215

jcg005@jefferson.edu

Facility Information:

Facility Name

Thomas Jefferson University Hospital

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

James C Gates

Phone

215-955-6215

jcg005@jefferson.edu

12. IPD Sharing Statement

Learn more about this trial

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

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