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

Browse trials for

• Hyperplasia 891
• Mouth Neoplasms 377
• Leukoplakia, Oral 42

Hyperplasia

891 studies on the registry are indexed under Hyperplasia; 103 are open to participants now.

This study's enrollment of 26 is below the median of 82 across 613 interventional studies indexed under Hyperplasia.

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Study arms

• Experimental
  Prevention (extended-release metformin hydrochloride)

  Patients receive extended-release metformin hydrochloride PO QD for 2 weeks and then BID for 10-12 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

  Other: Laboratory Biomarker Analysis · Drug: Metformin Hydrochloride

Interventions

• OtherLaboratory Biomarker Analysis

  Correlative studies

• DrugMetformin Hydrochloride

  Given PO

  Also known as: APO-Metformin, Cidophage, Dimefor, Glifage, Glucoformin, Glucophage, Glucophage ER, Metformin HCl, Riomet, Siofor

Primary outcomes

1. Clinical Response to Metformin Intervention

   Number of participants with complete and partial clinical response to metformin intervention. Criteria for complete and partial clinical response are: Complete Response (CR): Disappearance of all evidence of lesion(s). Partial Response (PR): Greater than or equal to 50% reduction in the sum of the products of diameters of lesion(s) measurable at baseline. Non-measurable lesion(s) may not increase greater than or equal to 25% in size and no new lesion may appear.

   Time frame: Baseline to up to 14 weeks

Secondary outcomes

1. Histologic Response to Metformin Intervention

   Number of participants with complete and partial histologic response to metformin intervention. Criteria for complete and partial histologic response are: Complete Response (CR): Complete reversal of dysplasia or hyperplasia to normal epithelium in the target lesion. Partial Response (PR): Improvement of the degree of dysplasia or hyperplasia in the target lesion.

   Time frame: Baseline to up to 14 weeks

2. Changes in Cell Proliferation and Its Molecular Targets

   Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers.

   Time frame: Baseline to up to 14 weeks

3. Changes in Frequent Dysregulated Molecular Mechanisms and OCT Expression

   Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers. A univariate logistic regression model with the clinical response as the outcome variable will be fitted to explore if any of the expression of frequent dysregulated mechanisms and OCT3 level are associated with the clinical response to metformin hydrochloride.

   Time frame: Baseline to up to 14 weeks

4. Impact of Genomic Alterations on the Biological and Biochemical Consequences and Clinical Response to Metformin Hydrochloride

   Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers. A univariate logistic regression model with the clinical response as the outcome variable will be fitted to explore if any genomic alterations are associated with the clinical response to metformin hydrochloride.

   Time frame: Up to 14 weeks

5. Change in Measurements of Metformin Hydrochloride Concentrations in Serum and Saliva

   Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers.

   Time frame: Baseline to up to 14 weeks

6. Change in Serum Metabolic Markers

   Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers.

   Time frame: Baseline to up to 14 weeks

7. Change in Serum and Saliva Inflammatory and Angiogenic Cytokines

   Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers.

   Time frame: Baseline to up to 14 weeks

Other outcomes

1. Change in Saliva Microbiome Analyzed Using Flow Cytometry

   This will characterize changes in the saliva microbiome before and after metformin intervention, including both the absolute microbial load and taxonomic composition. Will first evaluate changes in alpha diversity among matched pairs using non-parametric analogous Wilcoxon rank-sum test (Mann-Whitney test). To test for significant differences in beta diversity (e.g. if pretreatment and post-treatment samples cluster in principle coordinates analysis space), permutational multivariate analysis of variance (PERMANOVA) will be used.

   Time frame: Baseline to up to 14 weeks

2. Microbiome Signatures Correlated With Treatment Response

   Will first evaluate changes in alpha diversity among matched pairs using non-parametric analogous Wilcoxon rank-sum test (Mann-Whitney test). To test for significant differences in beta diversity (e.g. if pretreatment and post-treatment samples cluster in principle coordinates analysis space), PERMANOVA will be used.

   Time frame: Baseline to up to 14 weeks

Baseline characteristics

Publications

• Gutkind JS, Molinolo AA, Wu X, Wang Z, Nachmanson D, Harismendy O, Alexandrov LB, Wuertz BR, Ondrey FG, Laronde D, Rock LD, Rosin M, Coffey C, Butler VD, Bengtson L, Hsu CH, Bauman JE, Hewitt SM, Cohen EE, Chow HS, Lippman SM, Szabo E. Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions. JCI Insight. 2021 Sep 8;6(17):e147096. doi: 10.1172/jci.insight.147096. PubMed 34255745 ↗

Study documents

• Protocol and statistical analysis plan · Jul 6, 2018

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