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

NCT02581137 | Active Not Recruiting Phase 2 Results DMC

• 7 other identifiers: NCI-2015-01733HHSN2612012000311N01-CN-2012-000311510157567UAZ2015-05-02N01CN00031P30CA023074
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 4

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.

Conditions

Erythroplakia; Oral Cavity Carcinoma; Oral Leukoplakia; Hyperplasia

Outcome Measures

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.

  Baseline to up to 14 weeks

Secondary Outcomes (7)

• Histologic Response to Metformin Intervention

  Baseline to up to 14 weeks

• Changes in Cell Proliferation and Its Molecular Targets

  Baseline to up to 14 weeks

• Changes in Frequent Dysregulated Molecular Mechanisms and OCT Expression

  Baseline to up to 14 weeks

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

  Up to 14 weeks

• Change in Measurements of Metformin Hydrochloride Concentrations in Serum and Saliva

  Baseline to up to 14 weeks

Other Outcomes (2)

• Change in Saliva Microbiome Analyzed Using Flow Cytometry

  Baseline to up to 14 weeks

• Microbiome Signatures Correlated With Treatment Response

  Baseline to up to 14 weeks

Study Arms (1)

Prevention (extended-release metformin hydrochloride)

EXPERIMENTAL

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

Metformin Hydrochloride DRUG

Given PO

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

Prevention (extended-release metformin hydrochloride)

Laboratory Biomarker Analysis OTHER

Correlative studies

Prevention (extended-release metformin hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with oral leukoplakia or erythroplakia with mild, moderate, or severe histologic dysplasia, or hyperplasia not associated with mechanical factors such as ill-fitted dentures
• Measurable disease - minimum lesion size of 8 x 3 mm before initial biopsy
• Karnofsky performance status \>= 70%
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count \>= 1,000/microliter
• Platelets \>= 100,000/microliter
• Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\<1.5 × institutional ULN
• eGFR \> 40 mL/min using the Cockcroft-Gault equation
• Life expectancy \> 3 months
• Willing to use adequate contraception (barrier method, abstinence, subject has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation
• Ability to take oral medication
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients with diabetes who are taking insulin or oral agents
• History of diabetic ketoacidosis
• Participants may not be receiving any other investigational agents within past 3 months
• History of allergic reactions attributed to compounds of similar chemical composition to metformin or prior use of metformin within the last year
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, human immunodeficiency virus (HIV)-positive, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Oral carcinoma in situ
• History of chronic alcohol use or abuse defined as any one of the following: a) average consumption of 3 or more alcohol containing beverages daily in the past 12 months; b) consumption of 7 or more alcoholic beverages within a 24 hour (hr) period in the past 12 months
• Glycated hemoglobin (HbA1c) \> 8%
• Pregnancy or nursing women
• Acute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension
• History of renal disease
• History of prior head and neck squamous cell carcinoma (HNSCC) unless curatively treated for \>= 1 year
• Have received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 2 years; ongoing adjuvant hormonal therapy for breast cancer is allowed

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

BC Cancer Research Centre

Vancouver, British Columbia, V5Z 1L3, Canada

Location

University of British Columbia Hospital

Vancouver, British Columbia, V6T 2B5, Canada

Location

Related Publications (1)

• 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.

  PMID: 34255745 DERIVED

MeSH Terms

Conditions

Erythroplasia; Hyperplasia; Mouth Neoplasms; Leukoplakia, Oral

Interventions

Metformin

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Head and Neck Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases; Leukoplakia; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. Sherry Chow
• Organization: University of Arizona

schow@azcc.arizona.edu

5206263358

Study Officials

• Scott M Lippman

  The University of Arizona Medical Center-University Campus

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2015
• First Posted: October 20, 2015
• Study Start: June 10, 2016
• Primary Completion: October 12, 2017
• Study Completion (Estimated): December 19, 2026
• Last Updated: April 13, 2026
• Results First Posted: May 23, 2019

Record last verified: 2025-12

Locations

US (2); CA (2)