Summary

Eligibility
for people ages 21 years and up (full criteria)
Location
at San Diego, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Scott M. Lippman
Headshot of Scott M. Lippman
Scott M. Lippman

Description

Summary

This phase II trial tests whether metformin works in preventing oral cancer in patients with oral leukoplakia (white patches) or erythroplakia (red patches). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in the blood. It decreases the amount of glucose patients absorb from food and the amount of glucose made by the liver. Metformin also increases the body's response to insulin, a natural substance that controls the amount of glucose in the blood. This trial may help researchers determine if metformin can stop changes in the mouth that are related to pre-cancer growths in the mouth.

Official Title

M4OC-Prevent 2.0: Phase IIb Trial of Metformin for Oral Cancer Prevention

Details

PRIMARY OBJECTIVE: I. To determine the histological response to extended release metformin hydrochloride (metformin) intervention in the target lesion. SECONDARY OBJECTIVES: I. Clinical response to metformin intervention in the target lesion. II. Effect of metformin on cell proliferation (Ki67) and its molecular targets (pS6 and nuclear YAP) in the target lesion. III. Metformin effect on serum metabolic markers (C-peptide, glucose and HbA1c). IV. Trough plasma metformin concentrations. EXPLORATORY OBJECTIVES: I. Expression of dysregulated molecular mechanisms in the target lesion, including, in order of priority, p53, PTEN, p16, EGFR, and pEGFR. II. Immune cell infiltration and markers of inflammation in the target lesion. III. Analysis of genomic alterations in the target lesion and blood deoxyribonucleic acid (DNA). IV. Microbiome in oral rinses. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive extended release metformin hydrochloride orally (PO) once daily (QD) for 24 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive a placebo PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for up to 3 weeks.

Keywords

Erythroplakia Oral Leukoplakia Mouth Neoplasms Leukoplakia Leukoplakia, Oral Erythroplasia Metformin Extended Release Metformin Hydrochloride extended release metformin

Eligibility

You can join if…

Open to people ages 21 years and up

  • Participants with oral leukoplakia or erythroplakia with mild, moderate, or severe histologic dysplasia or hyperplasia at the high risk sites (e.g., floor of mouth, tongue). Lesions arising from the radiation field are excluded as study lesions.
  • Measurable disease - minimum lesion size of 8x3 mm before initial biopsy
  • Age >= 21 years
  • Current and former smokers (>= 5 packs in the lifetime)
  • Karnofsky performance scale >= 70%
  • Leukocytes >= 3,000/microliter
  • Absolute neutrophil count >= 1,000/microliter
  • Platelets >= 100,000/microliter
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional ULN
  • Estimation glomerular filtration rate (eGFR) > 45 mL/min (eGFR calculated using the equation Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine)
  • Willing to use adequate contraception (barrier method, abstinence, subject or partner has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation because the effects of metformin on the developing human fetus are unknown even though it is not teratogenic in rats and rabbits at 2-6 times the maximum recommended human daily dose. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
  • Ability to take oral medication
  • Ability to understand and the willingness to sign a written informed consent document

You CAN'T join if...

  • Patients with diabetes who are being treated with insulin or an anti-diabetic medication
  • 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
  • Hemoglobin A1c (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
  • Have received hormone therapy, chemotherapy, immunotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) within the past 18 months. History of prior curatively treated cancer is allowed as long as all primary and adjuvant treatment is completed >= 18 months prior to enrollment. Ongoing adjuvant hormonal treatment (e.g., for breast cancer) is allowed
  • Current use of carbonic anhydrase inhibitors (e.g. topiramate, zonisamide, acetazolamide, or dichlorphenamide)

Locations

  • UC San Diego Medical Center - Hillcrest
    San Diego California 92103 United States
  • University of Arizona Cancer Center-North Campus
    Tucson Arizona 85719 United States

Lead Scientist at UCSD

  • Scott M. Lippman
    Professor, Medicine, Vc-health Sciences-schools. Authored (or co-authored) 561 research publications

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
National Cancer Institute (NCI)
ID
NCT05237960
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 86 study participants
Last Updated