Metformin for Oral Leukoplakia/Erythroplakia Prevention
Recruiting in Palo Alto (17 mi)
+10 other locations
Overseen byScott M Lippman
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Arizona
Must not be taking: Insulin, Anti-diabetics, Investigational agents, Carbonic anhydrase inhibitors
Disqualifiers: Diabetes, Oral carcinoma, Liver disease, others
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests if metformin can prevent oral cancer in patients with pre-cancerous mouth patches. Metformin is a diabetes drug that controls blood sugar and may stop these patches from becoming cancerous. Metformin, widely used as a diabetes medication, has recently been reported to reduce cancer risk and improve outcomes in certain cancers.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using insulin, anti-diabetic medications, or certain other drugs like carbonic anhydrase inhibitors or ranolazine.
What data supports the effectiveness of the drug Metformin for preventing oral leukoplakia/erythroplakia?
Research suggests that Metformin, commonly used for type 2 diabetes, may help prevent the progression of oral lesions to cancer, as seen in lab and animal studies. However, clinical data on its effectiveness in reducing cancer risk in head and neck areas is mixed.
12345Is Metformin generally safe for humans?
There is no specific safety data on Metformin for oral leukoplakia/erythroplakia prevention in the provided research articles, but Metformin is a well-known medication commonly used to treat type 2 diabetes and is generally considered safe for humans when used as prescribed.
678910How is the drug metformin unique for preventing oral leukoplakia/erythroplakia?
Metformin, commonly used for type 2 diabetes, is unique in this context because it may prevent the progression of oral lesions to cancer by affecting cellular pathways, such as downregulating the epidermal growth factor receptor (EGFR), which is involved in cancer progression. This potential anticancer effect is separate from its role in controlling blood sugar levels.
1341112Eligibility Criteria
Adults over 21 with oral leukoplakia or erythroplakia, not caused by radiation, and certain health criteria met (e.g., kidney function). Smokers are eligible. Excludes those allergic to metformin, heavy alcohol users, recent cancer treatments other than skin/certain organ-confined cancers, uncontrolled diseases, pregnant/nursing women.Inclusion Criteria
I have oral leukoplakia or erythroplakia with abnormal cell growth in high-risk areas, but not from radiation.
Platelets >= 100,000/microliter
I can take pills by mouth.
+15 more
Exclusion Criteria
I have had allergic reactions to metformin or similar drugs, or I've used metformin in the last year.
I haven't had cancer treatments, except for hormone therapy, in the last 18 months.
I am currently taking medication like topiramate or ranolazine.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive extended release metformin or placebo orally once daily for 24 weeks
24 weeks
Biopsies and blood collections at baseline and week 24
Follow-up
Participants are monitored for safety and effectiveness after treatment
3 weeks
Participant Groups
This trial is testing if extended-release metformin can prevent oral cancer in patients with white or red patches in their mouth. Participants will either receive metformin or a placebo while undergoing biopsies and biospecimen collection to monitor changes.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm I (extended release metformin)Experimental Treatment3 Interventions
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.
Group II: Arm II (placebo)Placebo Group3 Interventions
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.
Extended Release Metformin Hydrochloride is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
πͺπΊ Approved in European Union as Metformin for:
- Type 2 diabetes
- Polycystic ovary syndrome
πΊπΈ Approved in United States as Metformin for:
- Type 2 diabetes
- Polycystic ovary syndrome
- Gestational diabetes
π¨π¦ Approved in Canada as Metformin for:
- Type 2 diabetes
- Polycystic ovary syndrome
π―π΅ Approved in Japan as Metformin for:
- Type 2 diabetes
π¨π³ Approved in China as Metformin for:
- Type 2 diabetes
π¨π Approved in Switzerland as Metformin for:
- Type 2 diabetes
- Polycystic ovary syndrome
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dalhousie University-Victoria General HospitalHalifax, Canada
University of Minnesota/Masonic Cancer CenterMinneapolis, MN
University of Michigan Comprehensive Cancer CenterAnn Arbor, MI
NYU College of DentistryNew York, NY
More Trial Locations
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Who Is Running the Clinical Trial?
University of ArizonaLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Metformin Prevents the Progression of Dysplastic Mucosa of the Head and Neck to Carcinoma in Nondiabetic Patients. [2019]Metformin is an oral anti-hyperglycemic agent used to treat type 2 diabetes mellitus (DM). In vitro and animal models have shown that metformin can prevent the progression of oral lesions to carcinoma; however, there is conflicting data in the clinical literature regarding risk reduction for malignancy in head and neck cancer (HNC).
The diagnosis and treatment of precancerous lesions. [2005]Leukoplakia is the most common premalignant lesion of the oral mucosa. The term should be used only for white lesions that cannot be characterised as any other definable lesion. The chance of malignant transformation can to some extent be predicted on the basis of the clinical appearance, the oral subsite, and the histopathological findings in the biopsy. The management of patients with oral leukoplakia is primarily directed towards elimination of possible causative factors. If the lesion persists, treatment is recommended in most cases. Of the various available treatment modalities no one is superior to the others. Both treated and untreated patients should be scheduled for long term follow-up, probably life long, with 6-12 month intervals in order to he able to detect possible recurrences in an early stage. Erythroplakia is less common than leukoplakia, but carries a considerably higher risk of malignant transformation. Therefore, erythroplakias should always be removed and subsequently, followed up.
Metformin may reduce oral cancer risk in patients with type 2 diabetes. [2018]Whether metformin use may affect the risk of oral cancer required further investigation.
Metformin Downregulates the Expression of Epidermal Growth Factor Receptor Independent of Lowering Blood Glucose in Oral Squamous Cell Carcinoma. [2022]Type 2 diabetes mellitus (T2DM) is among the risk factors for the occurrence and development of cancer. Metformin is a potential anticancer drug. Epidermal growth factor receptor (EGFR) plays an important role in the progression of oral squamous cell carcinoma(OSCC), but the relationship between metformin and EGFR expression in OSCC remains unclear.
PPARΞ³-Mediated p21 Induction in Aerodigestive Preneoplastic Cell Lines. [2022]Oral leukoplakia is defined as a mucous membrane disorder characterized by white patches that cannot be scraped off. Leukoplakia is the most frequent, potentially premalignant oral mucosa disorder and a good candidate for chemopreventive therapies. Pioglitazone activates peroxisome proliferator-activated receptor gamma (PPARΞ³), which forms a complex with nuclear cofactors and regulates gene expression of a variety of cell-cycle proteins and is currently being tested preclinically and clinically in aerodigestive cancer prevention.
[Oral toxicity of targeted anticancer therapies]. [2022]While toxicity of targeted anticancer therapies on the oral mucosa seems relatively frequent in clinical practice, it has not been properly characterized to date, apart from aphthous-like lesions due to mTOR inhibitors. Herein, we report the main oral lesions associated with these new therapies, with a description of the most frequent but also the most characteristic clinical manifestations of these drugs, such as anti-EGFR-induced mucositis, BRAF-inhibitor-associated hyperkeratosis, benign migratory glossitis and osteonecrosis of the jaw observed with angiogenesis inhibitors, as well as lesions more specifically linked with imatinib.
Efficacy and safety of topical administration of tacrolimus in oral lichen planus: An updated systematic review and meta-analysis of randomized controlled trials. [2022]Symptomatic oral lichen planus is a common chronic T-cell-mediated disorder characterized by pain and inflammation. The meta-analysis aimed to compare and evaluate the effects and safety of tacrolimus for treating patients with symptomatic oral lichen planus.
Strategies for the management of adverse events associated with mTOR inhibitors. [2022]Mammalian target of rapamycin (mTOR) inhibitors are used as potent immunosuppressive agents in solid-organ transplant recipients (everolimus and sirolimus) and as antineoplastic therapies for various cancers (eg, advanced renal cell carcinoma; everolimus, temsirolimus, ridaforolimus). Relevant literature, obtained from specific PubMed searches, was reviewed to evaluate the incidence and mechanistic features of specific adverse events (AEs) associated with mTOR inhibitor treatment, and to present strategies to effectively manage these events. The AEs examined in this review include stomatitis and other cutaneous AEs, wound-healing complications (eg, lymphocele, incisional hernia), diabetes/hyperglycemia, dyslipidemia, proteinuria, nephrotoxicity, delayed graft function, pneumonitis, anemia, hypertension, gonadal dysfunction, and ovarian toxicity. Strategies for selecting appropriate patients for mTOR inhibitor therapy and minimizing the risks of AEs are discussed, along with best practices for identifying and managing side effects. mTOR inhibitors are promising therapeutic options in immunosuppression and oncology; most AEs can be effectively detected and managed or reversed with careful monitoring and appropriate interventions.
Pembrolizumab-Induced Immune-Mediated Glossitis. [2022]Pembrolizumab (Keytruda), an anti-PD-1 antibody used in the treatment of several different malignancies has been identified to cause adverse effects pertaining to multiple body systems which include respiratory, gastrointestinal, dermatologic, and endocrine manifestations known as immune-related adverse events (IRAEs). Skin manifestations have been most described in current literature highlighting the most common adverse effects of this agent. However, adverse outcomes involving the oral mucosa have been rarely identified in the PD-1 and PD-L1 inhibitor classes of immunotherapeutic agents. We present a case of a 71-year-old male who was treated with a chemotherapeutic regimen including pembrolizumab for newly diagnosed squamous cell carcinoma of the lung, who later developed ulcerations on his tongue that were consistent with glossitis. Upon determining that this adverse effect may be immune-related, the patient was treated with oral prednisone 40 mg with a 10 mg taper each subsequent week, which resulted in significant improvement in the patient's symptoms following one month of treatment.
Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors. [2022]Development of biological targeted therapies and immune checkpoint inhibitors has redefined the treatment for many cancers; however, the increasing use of new protocols has led to physicians observing a new spectrum of toxicities. To date, oral adverse events induced by these new anticancer therapies have been mainly reported using nonspecific terminology ("stomatitis," "mucosal inflammation," "mucositis") and remain poorly characterized, with the exception of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis. Oral toxicities of targeted therapies often display very characteristic features which clearly differ from classic oral injuries observed with cytotoxic chemotherapy and/or radiotherapy. In addition, they frequently affect more than 20% of treated patients and can lead to a significant morbidity or permanent treatment discontinuation. Oral mucosal toxicities described in this review include mTOR inhibitor-associated stomatitis (mIAS); stomatitis, benign migratory glossitis, and osteonecrosis of the jaw associated with multi-targeted kinase inhibitors of the VEGF and PDGF receptors; mucositis induced by EGFR inhibitors (in monotherapy or in combination with head and neck radiotherapy and/or chemotherapy); hyperkeratotic lesions with BRAF inhibitors; pigmentary changes and lichenoid reactions secondary to imatinib; and more recent data on the "Osler-Weber-Rendu-like syndrome" described with the antibody-drug conjugate, TDM-1. Finally, we provide, to our knowledge, the first available structured data on oral toxicities induced by the new recently FDA- and EMA-approved monoclonal antibodies targeting PD-1. Clinical management of these targeted therapy-related oral changes is also discussed.
Metformin extended release for the treatment of type 2 diabetes mellitus. [2019]Metformin extended release (ER) (Glumetza, Depomed, Inc.) is a recently approved formulation that provides effective and well-tolerated glycaemic control with once-daily dosing. Metformin ER has similar bioavailability to conventional immediate-release (IR) formulations. In controlled clinical trials, metformin ER provided effective glycaemic control for 24 weeks when administered either as monotherapy or in combination with sulfonylurea. Good glycaemic control was maintained for an additional 24 weeks during an open-label extension study. Once-daily dosing with metformin ER 1500 mg/day was as effective as twice-daily dosing with metformin IR at the same total daily dose. Metformin ER was well tolerated at doses of 1500 or 2000 mg/day, with no increase in the frequency or severity of adverse events at the higher dose.
Clinical development of metformin extended-release tablets for type 2 diabetes: an overview. [2013]Glumetz (Depomed, Inc., Menlo Park, CA, USA) is a recently approved gastric retentive extended-release formulation of metformin (M-ER) that provides effective, sustained and well-tolerated glycemic control with once daily administration. Pharmacokinetic studies have demonstrated a similar bioavailability of M-ER administered once daily to immediate-release metformin given twice daily. In addition, M-ER has demonstrated a nearly linear dose proportionality with a relative bioavailability of highest dose to lowest dose of 80%, whereas with immediate-release metformin the relative bioavailability of the highest dose to the lowest dose is only 58%. M-ER demonstrated a positive food effect and should be administered with a meal, preferably the evening meal. Because metformin is only eliminated through renal mechanisms, the use of M-ER, as is the case with other formulations, is contraindicated in patients with renal impairment. Administration of M-ER with sulfonylureas (SUs) had no effect on the pharmacokinetics of metformin. In controlled clinical trials M-ER demonstrated efficacy for 24 weeks as a monotherapy or in combination with SU. Additionally, glycemic control was maintained for an extra 24 weeks in an open-label monotherapy extension study of M-ER. M-ER was well tolerated in all studies.