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
Sponsored by
About this trial
This is an interventional prevention trial for Erythroplakia
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
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
No
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
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.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Change in lesion status
Description
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.
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
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.
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
No
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
Email
Andrew.Yampolsky@jefferson.edu
First Name & Middle Initial & Last Name or Official Title & Degree
James Gates, DMD, MD
Phone
215-955-6215
Email
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
Email
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
We'll reach out to this number within 24 hrs