Trial Outcomes & Findings for Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion (NCT NCT02581137)

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

Baseline to up to 14 weeks

Results posted on

2025-06-29

Participant Flow

Participant milestones

Participant milestones
Measure	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. Laboratory Biomarker Analysis: Correlative studies Metformin Hydrochloride: Given PO
Overall Study STARTED	26
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prevention (Extended-release Metformin Hydrochloride) n=26 Participants 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
Age, Continuous	58 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment Canada	12 Participants n=5 Participants
Region of Enrollment United States	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to up to 14 weeks

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.

Outcome measures

Outcome measures
Measure	Prevention (Extended-release Metformin Hydrochloride) n=23 Participants 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
Clinical Response to Metformin Intervention	4 Participants

SECONDARY outcome

Timeframe: Baseline to up to 14 weeks

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.

Outcome measures

Outcome measures
Measure	Prevention (Extended-release Metformin Hydrochloride) n=23 Participants 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
Histologic Response to Metformin Intervention	14 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 14 weeks

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 14 weeks

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.

Outcome measures

Outcome data not reported

Adverse Events

Prevention (Extended-release Metformin Hydrochloride)

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Prevention (Extended-release Metformin Hydrochloride) n=26 participants at risk 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
Gastrointestinal disorders oral pain	3.8% 1/26 • 12 weeks

Other adverse events

Other adverse events
Measure	Prevention (Extended-release Metformin Hydrochloride) n=26 participants at risk 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
Gastrointestinal disorders Abdominal pain	7.7% 2/26 • 12 weeks
Gastrointestinal disorders Bloating	7.7% 2/26 • 12 weeks
Gastrointestinal disorders Diarrhea	50.0% 13/26 • 12 weeks
Gastrointestinal disorders Gastrointestinal pain	7.7% 2/26 • 12 weeks
Gastrointestinal disorders Nausea	53.8% 14/26 • 12 weeks
Gastrointestinal disorders Oral pain	7.7% 2/26 • 12 weeks
Gastrointestinal disorders Stomach pain	15.4% 4/26 • 12 weeks
Gastrointestinal disorders Vomiting	15.4% 4/26 • 12 weeks
General disorders Fatigue	15.4% 4/26 • 12 weeks
Infections and infestations Upper respiratory infection	7.7% 2/26 • 12 weeks
Nervous system disorders Dizziness	23.1% 6/26 • 12 weeks
Nervous system disorders Headache	15.4% 4/26 • 12 weeks
Skin and subcutaneous tissue disorders Rash acneiform	7.7% 2/26 • 12 weeks

Additional Information

Dr. Sherry Chow

University of Arizona

Phone: 5206263358

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60