Metformin for the Prevention of Oral Cancer in Patients With Oral Leukoplakia or Erythroplakia
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|ClinicalTrials.gov Identifier: NCT05237960|
Recruitment Status : Recruiting
First Posted : February 14, 2022
Last Update Posted : March 30, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Erythroplakia Oral Leukoplakia||Procedure: Biopsy Procedure: Biospecimen Collection Drug: Extended Release Metformin Hydrochloride Drug: Placebo Administration||Phase 2|
I. To determine the histological response to metformin hydrochloride (metformin) intervention in the target lesion.
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.
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. Patients also undergo collection of blood and biopsy at baseline and week 24.
ARM II: Patients receive a placebo PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and biopsy at baseline and week 24.
After completion of study treatment, patients are followed for up to 3 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||86 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||M4OC-Prevent 2.0: Phase IIb Trial of Metformin for Oral Cancer Prevention|
|Actual Study Start Date :||November 28, 2022|
|Estimated Primary Completion Date :||July 31, 2026|
|Estimated Study Completion Date :||July 31, 2026|
Experimental: Arm I (extended release metformin)
Patients receive extended release metformin hydrochloride PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients will also undergo biopsies and blood collections on study.
Procedure: Biospecimen Collection
Drug: Extended Release Metformin Hydrochloride
Placebo Comparator: Arm II (placebo)
Patients receive a placebo PO QD for 24 weeks in the absence of disease progression or unacceptable toxicity. Patients will also undergo biopsies and blood collections on study.
Procedure: Biospecimen Collection
Drug: Placebo Administration
- Histologic response to metformin [ Time Frame: Up to 24 weeks ]Histologic response will be evaluated by the following criteria: 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. No change (NC): No change in the degree of dysplasia or hyperplasia in the target lesion, anything that is not CR, PR or PD. Progressive disease (PD): Increase in the severity of grade of histology in the target lesion.
- Clinical response to metformin [ Time Frame: Up to 24 weeks ]Clinical response will be evaluated by the following criteria: CR: disappearance of all evidence of lesion(s). 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. NC: no change in the size of the lesion(s) identified at baseline and no new lesions appearing, i.e., anything that is not CR, PR, or PD. PD: any increase greater than or equal to 25% in the product of the diameters of any lesion(s) measurable at baseline or in the estimated size of lesion(s) nonmeasurable at baseline or the appearance of an unequivocal new lesion.
- Cell proliferation [ Time Frame: Up to 24 weeks ]Effect of metformin on cell proliferation (Ki67) and its molecular targets (pS6 and nuclear YAP) in the target lesion. The change (pre to post) will be compared between arms.
- Serum metabolic markers [ Time Frame: Up to 24 weeks ]Metformin effect on serum metabolic markers (C-peptide, glucose and HbA1c). The change (pre to post) in serum metabolic markers will be compared between arms.
- Plasma metformin concentrations [ Time Frame: From baseline, up to 24 weeks ]The plasma metformin concentrations will be determined in the pre- and post-intervention samples.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||21 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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. 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 < 20 years would most likely not have oral leukoplakia
- 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.
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05237960
|United States, Arizona|
|University of Arizona Cancer Center-North Campus||Recruiting|
|Tucson, Arizona, United States, 85719|
|Contact: Shethal Bearelly 520-626-5054 firstname.lastname@example.org|
|Principal Investigator: Shethal Bearelly|
|United States, California|
|UC San Diego Medical Center - Hillcrest||Not yet recruiting|
|San Diego, California, United States, 92103|
|Contact: Scott M. Lippman 858-822-1222 email@example.com|
|Principal Investigator: Scott M. Lippman|
|United States, Florida|
|Moffitt Cancer Center||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Christine H. Chung 813-745-5431 firstname.lastname@example.org|
|Principal Investigator: Christine H. Chung|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute||Not yet recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Jennifer Gross 404-778-0278 Jhgros3@emory.edu|
|Principal Investigator: Jennifer Gross|
|United States, Louisiana|
|Louisiana State University||Not yet recruiting|
|Lafayette, Louisiana, United States, 70503|
|Contact: Cherie-Ann O. Nathan 318-675-6262 email@example.com|
|Principal Investigator: Cherie-Ann O. Nathan|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Not yet recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Justine Moe 734-963-5963 firstname.lastname@example.org|
|Principal Investigator: Justine Moe|
|United States, Minnesota|
|University of Minnesota/Masonic Cancer Center||Not yet recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Frank G. Ondrey 612-625-3200 email@example.com|
|Principal Investigator: Frank G. Ondrey|
|United States, New York|
|NYU College of Dentistry||Not yet recruiting|
|New York, New York, United States, 10010|
|Contact: Alexander R. Kerr 212-998-9885 firstname.lastname@example.org|
|Principal Investigator: Alexander R. Kerr|
|Canada, British Columbia|
|British Columbia Cancer Agency||Not yet recruiting|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Contact: Miriam Rosin 604-675-8061 email@example.com|
|Principal Investigator: Miriam Rosin|
|Canada, Nova Scotia|
|Dalhousie University||Not yet recruiting|
|Halifax, Nova Scotia, Canada, B3H 4R2|
|Contact: Leigha Rock firstname.lastname@example.org|
|Principal Investigator: Leigha Rock|
|Principal Investigator:||Scott M Lippman||University of California, San Diego Moores Cancer Center|
|Responsible Party:||University of Arizona|
|Other Study ID Numbers:||
NCI-2022-00596 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Pending12 ( Other Identifier: University of Arizona Cancer Center - Prevention Research Clinic )
UAZ21-07-01 ( Other Identifier: DCP )
P30CA023074 ( U.S. NIH Grant/Contract )
UG1CA242596 ( U.S. NIH Grant/Contract )
|First Posted:||February 14, 2022 Key Record Dates|
|Last Update Posted:||March 30, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Head and Neck Neoplasms
Neoplasms by Site
Pathological Conditions, Anatomical
Physiological Effects of Drugs