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  • Cancer Type: Head & Neck
  • Study Type: Prevention
  • NCT#: NCT05237960
  • Phase: Phase II
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  • Overview

    Study Title:

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


    This phase IIb 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.


    Primary Objective * To determine the histological response to metformin intervention in the target lesion. Secondary Objectives * Clinical response to metformin intervention in the target lesion * Effect of metformin on cell proliferation (Ki67) and its molecular targets (pS6 and nuclear YAP) in the target lesion * Metformin effect on serum metabolic markers

  • Treatments


    Therapy (NOS)


    Metformin/Placebo ()

  • Inclusion Criteria

      Inclusion Criteria:
    • 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. Oral proliferative verrucous leukoplakia (PVL) or proliferative verrucous hyperplasia are allowed.
    • Measurable disease - minimum lesion size of 8x3 mm before initial biopsy
    • Age >= 21 years. Adults 18-20 are not included as Canadian law prohibits purchase of cigarettes under the age of 21; investigators wish to keep criteria consistent among all trial sites. Also, smokers aged > Current and former use of tobacco products, with a minimum use of smokeless tobacco (such as snuff or chewing tobacco) at least 20 times OR combustible tobacco (such as cigarettes, cigars, or pipe smoking) equivalent to at least 100 cigarettes over one's lifetime. For cigarette equivalence, 1 cigar is considered equivalent to 4 cigarettes, and 1 pipe fill is considered equivalent to 3.5 cigarettes.
    • Karnofsky performance scale >= 70%
    • Lab values as outlined in protocol
    • 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.
    • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
    • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
    • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
    • Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
    • Ability to take oral medication
    • Ability to understand and the willingness to sign a written informed consent document in English or Spanish
    • Willing to avoid excessive alcohol consumption during the course of the study, defined as: For males: avoiding consumption of more than 14 drinks per week OR more than 4 drinks on a single occasion (defined as a 2-hour period) For females: avoiding consumption of more than 7 drinks per week OR more than 3 drinks on a single occasion (defined as a 2-hour period).
    • Other criteria may apply
  • Exclusion Criteria

      Exclusion Criteria:
    • 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 at screeining
    • 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 from the baseline biopsy
    • 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. Pregnant women are excluded from this study 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. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with metformin, breastfeeding should be discontinued
    • 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, including oral 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) or ranolazine
    • Other criteria may apply

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