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

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ClinicalTrials.gov Identifier: NCT02581137
Recruitment Status : Active, not recruiting
First Posted : October 20, 2015
Results First Posted : May 23, 2019
Last Update Posted : August 30, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Erythroplakia
Hyperplasia
Mild Dysplasia
Moderate Dysplasia
Oral Cavity Carcinoma
Oral Leukoplakia
Severe Dysplasia
Interventions Other: Laboratory Biomarker Analysis
Drug: Metformin Hydrochloride
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Prevention (Extended-release Metformin Hydrochloride)
Hide Arm/Group Description

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.

Laboratory Biomarker Analysis: Correlative studies

Metformin Hydrochloride: Given PO

Period Title: Overall Study
Started 26
Completed 22
Not Completed 4
Arm/Group Title Prevention (Extended-release Metformin Hydrochloride)
Hide Arm/Group Description

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.

Laboratory Biomarker Analysis: Correlative studies

Metformin Hydrochloride: Given PO

Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
58  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
14
  53.8%
Male
12
  46.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Hispanic or Latino
1
   3.8%
Not Hispanic or Latino
24
  92.3%
Unknown or Not Reported
1
   3.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   3.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   3.8%
White
23
  88.5%
More than one race
0
   0.0%
Unknown or Not Reported
1
   3.8%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Canada
12
  46.2%
United States
14
  53.8%
1.Primary Outcome
Title Clinical Response to Metformin Intervention
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Prevention (Extended-release Metformin Hydrochloride)
Hide Arm/Group Description:

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.

Laboratory Biomarker Analysis: Correlative studies

Metformin Hydrochloride: Given PO

Overall Number of Participants Analyzed 23
Measure Type: Count of Participants
Unit of Measure: Participants
4
  17.4%
2.Secondary Outcome
Title Histologic Response to Metformin Intervention
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Prevention (Extended-release Metformin Hydrochloride)
Hide Arm/Group Description:

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.

Laboratory Biomarker Analysis: Correlative studies

Metformin Hydrochloride: Given PO

Overall Number of Participants Analyzed 23
Measure Type: Count of Participants
Unit of Measure: Participants
14
  60.9%
3.Secondary Outcome
Title Changes in Cell Proliferation and Its Molecular Targets
Hide Description 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
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Changes in Frequent Dysregulated Molecular Mechanisms and OCT Expression
Hide Description 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
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Impact of Genomic Alterations on the Biological and Biochemical Consequences and Clinical Response to Metformin Hydrochloride
Hide Description 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
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Change in Measurements of Metformin Hydrochloride Concentrations in Serum and Saliva
Hide Description 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
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Change in Serum Metabolic Markers
Hide Description 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
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Change in Serum and Saliva Inflammatory and Angiogenic Cytokines
Hide Description 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
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title Change in Saliva Microbiome Analyzed Using Flow Cytometry
Hide Description 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
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Microbiome Signatures Correlated With Treatment Response
Hide Description 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
Outcome Measure Data Not Reported
Time Frame 12 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Prevention (Extended-release Metformin Hydrochloride)
Hide Arm/Group Description

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.

Laboratory Biomarker Analysis: Correlative studies

Metformin Hydrochloride: Given PO

All-Cause Mortality
Prevention (Extended-release Metformin Hydrochloride)
Affected / at Risk (%)
Total   0/26 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Prevention (Extended-release Metformin Hydrochloride)
Affected / at Risk (%)
Total   1/26 (3.85%) 
Gastrointestinal disorders   
oral pain   1/26 (3.85%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Prevention (Extended-release Metformin Hydrochloride)
Affected / at Risk (%)
Total   24/26 (92.31%) 
Gastrointestinal disorders   
Abdominal pain   2/26 (7.69%) 
Bloating   2/26 (7.69%) 
Diarrhea   13/26 (50.00%) 
Gastrointestinal pain   2/26 (7.69%) 
Nausea   14/26 (53.85%) 
Oral pain   2/26 (7.69%) 
Stomach pain   4/26 (15.38%) 
Vomiting   4/26 (15.38%) 
General disorders   
Fatigue   4/26 (15.38%) 
Infections and infestations   
Upper respiratory infection   2/26 (7.69%) 
Nervous system disorders   
Dizziness   6/26 (23.08%) 
Headache   4/26 (15.38%) 
Skin and subcutaneous tissue disorders   
Rash acneiform   2/26 (7.69%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Sherry Chow
Organization: University of Arizona
Phone: 5206263358
EMail: schow@azcc.arizona.edu
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02581137     History of Changes
Other Study ID Numbers: NCI-2015-01733
NCI-2015-01733 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
HHSN2612012000311
N01-CN-2012-00031
1510157567 ( Other Identifier: Banner University Medical Center - Tucson )
UAZ2015-05-02 ( Other Identifier: DCP )
N01CN00031 ( U.S. NIH Grant/Contract )
P30CA023074 ( U.S. NIH Grant/Contract )
First Submitted: October 19, 2015
First Posted: October 20, 2015
Results First Submitted: April 29, 2019
Results First Posted: May 23, 2019
Last Update Posted: August 30, 2019