Metformin for the Prevention of Oral Cancer in Patients With Oral Leukoplakia or Erythroplakia

PRIMARY OBJECTIVE: I. To determine the histological response to metformin hydrochloride (metformin) intervention in the target lesion. SECONDARY OBJECTIVES: I. Clinical response to metformin intervention in the target lesion. II. Effect of metformin on cell proliferation (Ki67) and its molecular targets (pS6 and nuclear YAP) in the target lesion. III. Metformin effect on serum metabolic markers (C-peptide, glucose and HbA1c). IV. Trough plasma metformin concentrations. EXPLORATORY OBJECTIVES: I. Expression of dysregulated molecular mechanisms in the target lesion, including, in order of priority, p53, PTEN, p16, EGFR, and pEGFR. II. Immune cell infiltration and markers of inflammation in the target lesion. III. Analysis of genomic alterations in the target lesion and blood deoxyribonucleic acid (DNA). IV. Microbiome in oral rinses. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive extended release metformin hydrochloride orally (PO) once daily (QD) for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and biopsy at baseline and week 24. ARM II: Patients receive a placebo PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and biopsy at baseline and week 24. After completion of study treatment, patients are followed for up to 3 weeks.