Metformin for the Prevention of Oral Cancer in Patients With Oral Premalignant Lesions
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
PRIMARY OBJECTIVE:
- To evaluate the transformation-free-survival in lesion types erythroplakia (EP) and verrucous hyperplasia (VH).
SECONDARY OBJECTIVE:
- 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:
- 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 Design
Arms and Interventions
| 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. |
Drug: Metformin
Given PO
Other Names:
Procedure: Biopsy
Undergo biopsy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Transformation-free-survival, in lesion types erythroplakia and verrucous hyperplasia [Up to 3 years]
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 [Baseline to 1 year after treatment]
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.
Other Outcome Measures
- Transformation-free-survival, in lesion types homogenous leukoplakia and non-homogenous leukoplakia [Up to 3 years]
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.
Eligibility Criteria
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
-
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:
-
Severe dysplasia, 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
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Frictional: sharp tooth
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Trauma
-
Immunosuppression by natural illness or medically induced
-
Hypersensitivity or allergic reaction to metformin or some other contraindication
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | United States | 19107 |
Sponsors and Collaborators
- Thomas Jefferson University
- National Cancer Institute (NCI)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 22D.296