Clinical Trial: Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: M4OC-Prevent: Metformin for Oral Cancer Prevention

Brief 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 Summary:

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 sa
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Change in clinical response of oral premalignant lesions [ Time Frame: Baseline to up to 14 weeks ]

Clinical response will be categorized into complete response (CR), partial response (PR), no change or progressive disease. A participant with CR or PR is considered as a respondent. A one-sided one-sample binomial exact test at a significance level of 5% will be performed to see if the clinical response rate is greater than 30% (poor treatment).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in histologic response [ Time Frame: Baseline to up to 14 weeks ]
    The histologic response rate will be calculated and a one-sided 95% confidence interval based on the exact method will be derived.
  • Change in measurements of metformin hydrochloride concentrations in serum and saliva [ Time Frame: Baseline to up to 14 weeks ]
    Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers.
  • Change in serum and saliva inflammatory and angiogenic cytokines [ Time Frame: Baseline to up to 14 weeks ]
    Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers.
  • Change in serum metabolic markers [ Time Frame: Baseline to up to 14 weeks ]
    Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers.
  • Changes in cell proliferation and its molecular targets [ Time Frame: Baseline to up to 14 weeks ]
    Nonparametric methods, e.g. signed rank test, will be performed to evaluate each of the changes in tissue, serum, and saliva markers.
  • Changes in frequent dysregulated molecular mechanisms and OCT expression [ Time Frame: Baseline to up to 14 weeks ]
    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.
  • Impact of genomic alterations on the biological and biochemical consequences and clinical response to metformin hydrochloride [ Time Frame: Up to 14 weeks ]
    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.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 19, 2015
Date Started: June 2016
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017