NCT02581137

Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion

M4OC-Prevent: Metformin for Oral Cancer Prevention

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase IIa trial studies how well metformin hydrochloride works in preventing oral cancer in patients with an oral premalignant lesion (oral leukoplakia or erythroplakia). Oral premalignant lesions look like red or whitish plaques or lesions in the mouth that do not rub off and can be associated with a higher risk of cancer. Metformin hydrochloride may help prevent oral cancer from forming in patients with an oral premalignant lesion.

Detailed description

PRIMARY OBJECTIVES: I. To determine the clinical response of oral premalignant lesions to 12-14 weeks of metformin (metformin hydrochloride) intervention. SECONDARY OBJECTIVES: I. Histologic response to metformin intervention in the target lesion. II. Tissue-based biomarkers: metformin effect on cell proliferation and its molecular targets in the target lesion and in the normal tissue (marker of cell proliferation, Ki67, molecular targets of metformin, including, in order of priority, phosphorylated ribosomal protein S6 kinase \[pS6\], phosphorylated v-akt murine thymoma viral oncogene homolog 1 \[pAKT\]S473, phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 \[p4EBP\], phosphorylated acetyl-CoA carboxylase alpha \[pACC\]). III. Tissue-based biomarkers: expression of dysregulated molecular mechanisms and organic cation transporter 3 (OCT 3) in the target lesion and in the normal tissue, including, in order of priority, epidermal growth factor receptor (EGFR), phosphorylated (p)EGFR, tumor protein 53 (p53), phosphatase and tensin homolog (PTEN), phosphorylated mitogen-activated protein kinase 1 (pERK), cyclin-dependent kinase inhibitor 2A (p16), and OCT3. IV. Tissue-based biomarkers: targeted analysis of cancer-associated genes in the target lesion and blood deoxyribonucleic acid (DNA). V. Serum and saliva based biomarkers: metformin effect on serum metabolic markers (C-peptide, glycosylated hemoglobin \[HbA1c\]). VI. Serum and saliva based biomarkers: metformin concentrations in serum and saliva. VII Serum and saliva based biomarkers: metformin effect on serum and saliva inflammatory and angiogenic cytokines, including interleukin (IL)-6, IL-8, growth-related oncogene-1 (GRO-1), and vascular endothelial growth factor (VEGF). EXPLORATORY OBJECTIVES: I. To characterize changes in the saliva microbiome before and after metformin intervention, including both the absolute microbial load and taxonomic composition. II. To evaluate the potential microbiome signatures that are correlated with treatment response. OUTLINE: Patients receive extended-release metformin hydrochloride orally (PO) once daily (QD) for 2 weeks and then twice daily (BID) for 10-12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 2-4 weeks.

Conditions

• Erythroplakia
• Hyperplasia
• Oral Cavity Carcinoma
• Oral Leukoplakia

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Metformin Hydrochloride	Given PO

Timeline

• Start date: 2016-06-10
• Primary completion: 2017-10-12
• Completion: 2026-12-19
• First posted: 2015-10-20
• Last updated: 2026-04-13
• Results posted: 2019-05-23

Locations

4 sites across 2 countries: United States, Canada