The following datasets contain the data available for EPPT UAZ2015-05-02. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Raw Datasets

These 25 datasets contain the raw form data received, excluding PII.

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Trial Summary

The study is a phase IIa trial in individuals with oral leukoplakia or erythroplakia to explore repurposing metformin for oral cancer prevention. Its primary objective is to determine the clinical response of oral premalignant lesions to 12-14 weeks of metformin intervention.

This trial has one arm:

• Arm I: Metformin (500mg/day for 1st week, 1000mg/day for 2nd week, 2000mg/day for remainder)

Enrollment Statistics

Actual Registration: 33

• 26 people administered treatment (26 of 33 registered)
  • 22 completed study (22 of 26 administered treatment)
  • 4 left study early (4 of 26 administered treatment)
    • 2 due to adverse events
    • 2 due to participant withdrawal
• 7 people were ineligible (7 of 33 registered)

Eligibility Criteria

Inclusion Criteria

• Participants with oral leukoplakia or erythroplakia with mild, moderate, or severe histologic dysplasia, or hyperplasia not associated with mechanical factors such as ill-fitted dentures.
• Measurable disease – minimum lesion size of 8x3 mm before initial biopsy.
• Age >=18 years.
• Karnofsky performance status >= 70%.
• Participants must have normal organ and marrow function as defined below:
  • Leukocytes >=3,000/microliter
  • Absolute neutrophil count >=1,000/microliter
  • Platelets >=100,000/microliter
  • Total bilirubin >=1.5 x institutional ULN
  • AST (SGOT)/ALT (SGPT) <=1.5 x institutional ULN
  • eGFR >40 mL/min using the Cockcroft-Gault equation
• Life expectancy > 3 months.
• Willing to use adequate contraception (barrier method, abstinence, subject has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation because the effects of metformin on the developing human fetus are unknown even though it is not teratogenic in rats and rabbits at 2-6 times the maximum recommended human daily dose.
• Ability to take oral medication.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Patients with diabetes who are taking insulin or oral agents.
• History of diabetic ketoacidosis.
• Participants may not be receiving any other investigational agents within past 3 months.
• History of allergic reactions attributed to compounds of similar chemical composition to metformin or prior use of metformin within the last year.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, HIV-positive, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Oral carcinoma in situ.
• History of chronic alcohol use or abuse defined as any one of the following: a) average consumption of 3 or more alcohol containing beverages daily in the past 12 months) consumption of 7 or more alcoholic beverages within a 24 hr period in the past 12 months.
• HbA1c > 8%.
• Pregnancy or nursing women.
• Acute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension.
• History of renal disease.
• History of prior HNSCC unless curatively treated for >= 1 year.
• Have received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 2 years. Ongoing adjuvant hormonal therapy for breast cancer is allowed.

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Results/Findings:

Twenty-three participants were evaluable for response. The clinical response rate (defined as ≥50% reduction in lesion size) was 17%. While lower than the proposed threshold for favorable clinical response, the histologic response rate (improvement in histologic grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared to never smokers, current and former smokers had statistically significantly increased histologic responses (p=0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layer of OPL and the histological (p=0.04) and clinical (p=0.01) responses.