Metformin for Preventing Oral Cancer

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Insulin, Oral diabetes agents

Disqualifiers: Diabetes, HIV, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12-14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether metformin hydrochloride, a medication commonly used for type 2 diabetes, can help prevent oral cancer in individuals with certain pre-cancerous mouth lesions. These lesions may appear as white or red patches that do not wipe away and could develop into cancer over time. Participants will take metformin to determine if it lowers their risk of developing oral cancer. This trial suits those with oral leukoplakia or erythroplakia (types of lesions) who are not currently managing diabetes with medication. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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 taking insulin or oral diabetes medications, or if you have used metformin in the past year.

Is there any evidence suggesting that metformin hydrochloride is likely to be safe for humans?

Research has shown that metformin hydrochloride is generally easy for people to take. The FDA has already approved it for treating type 2 diabetes, providing extensive knowledge about its safety in humans. Some studies suggest it might also reduce the risk of certain cancers, possibly by up to 23%.

In past studies, most participants taking metformin did not experience serious side effects. Common side effects are usually mild, such as an upset stomach or diarrhea, and these often improve as the body adjusts to the medication. It is important to discuss any side effects or concerns with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for oral cancer?

Unlike the standard treatments for oral cancer, which often involve surgery, radiation, and chemotherapy, metformin hydrochloride offers a novel approach by using a common diabetes medication in cancer prevention. Researchers are excited about metformin because it targets cancer cells through a different mechanism, potentially reducing their growth by affecting cellular metabolism. Additionally, as an oral medication, it provides a non-invasive option that could have fewer side effects compared to traditional therapies. This makes it a promising candidate for preventing oral cancer progression in a more patient-friendly way.

What evidence suggests that metformin hydrochloride might be an effective treatment for preventing oral cancer?

Research has shown that metformin hydrochloride, which participants in this trial will receive, might help prevent cancer. Reports indicate it can lower the risk of cancer by up to 23% worldwide. Studies have found that metformin can stop cancer cells from growing. Specifically, metformin may help prevent oral cancer in people with oral leukoplakia (white patches) or erythroplakia (red patches). These findings suggest that metformin could effectively stop oral cancer before it starts. ^{1 2 3 5 6}

Who Is on the Research Team?

Scott M Lippman

Principal Investigator

The University of Arizona Medical Center-University Campus

Are You a Good Fit for This Trial?

This trial is for people with certain mouth lesions that could turn into cancer, specifically oral leukoplakia or erythroplakia. Participants should have a life expectancy over 3 months, be able to take pills, and not have diabetes treated with insulin or other drugs. They must also agree to use birth control and not have had any recent treatments for other cancers.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

Measurable disease - minimum lesion size of 8 x 3 mm before initial biopsy

Leukocytes >= 3,000/microliter

Exclusion Criteria

I had head and neck cancer but was treated successfully over a year ago.

Participants may not be receiving any other investigational agents within past 3 months

I have diabetes and am taking insulin or pills for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive extended-release metformin hydrochloride orally once daily for 2 weeks and then twice daily for 10-12 weeks

12-14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin Hydrochloride

Trial Overview The study is testing if Metformin Hydrochloride can prevent mouth cancer in patients with premalignant lesions. It's a phase IIa trial where the effects of the drug will be monitored through lab tests to see if it stops these lesions from becoming cancerous.

How Is the Trial Designed?

Group I: Prevention (extended-release metformin hydrochloride) Experimental Treatment 2 Interventions

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.

Metformin Hydrochloride is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Metformin Hydrochloride for:

• Type 2 diabetes
• Polycystic ovary syndrome

Approved in United States as Metformin Hydrochloride for:

• Type 2 diabetes
• Polycystic ovary syndrome
• Gestational diabetes

Approved in Canada as Metformin Hydrochloride for:

• Type 2 diabetes
• Polycystic ovary syndrome

Approved in Japan as Metformin Hydrochloride for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A study involving over 300,000 patients with type 2 diabetes found that those who used metformin had a significantly lower risk of developing oral cancer compared to those who did not use metformin, with a hazard ratio of 0.584.

The protective effect of metformin against oral cancer increased with longer use, showing a dramatic reduction in risk for those who used it for more than 21.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin may reduce oral cancer risk in patients with type 2 diabetes. Tseng, CH.[2018]

In a case series of 3 nondiabetic patients with recurrent dysplastic lesions from head and neck cancer, adjuvant therapy with metformin resulted in complete or partial regression of lesions without the need for additional surgeries, indicating its potential efficacy in this context.

The study suggests that using metformin in nondiabetic patients may provide a clearer understanding of its effects on malignancy risk reduction, as these patients are not influenced by the complications associated with diabetes, such as increased cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Prevents the Progression of Dysplastic Mucosa of the Head and Neck to Carcinoma in Nondiabetic Patients. Lerner, MZ., Mor, N., Paek, H., et al.[2019]

In a study of 130 patients with type 2 diabetes treated with Metformin Hydrochloride, gastrointestinal adverse effects were the most common, with diarrhea affecting 30.77% of patients and leading to treatment discontinuation in 3.85%.

No cases of serious complications like lactic acidosis or allergic reactions were reported, indicating that while Metformin is generally safe, monitoring for digestive issues is important in managing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cross-Sectional Study on Adverse Effects of Metformin Hydrochloride on 130 Patients Type 2 Diabetic Admitted to Medical Center and Diabetes Home of Sidi Bel-Abbès]. Sakouhi, M., Matmour, D., Belakhdar, K., et al.[2023]

Metformin is an effective oral medication for treating non-insulin-dependent diabetes mellitus (type II diabetes) and does not cause hypoglycemia, which is a common side effect of other diabetes medications like sulfonylureas.

The drug is considered safe when proper precautions are taken, including monitoring liver and kidney function, and it has gained widespread use internationally, recently receiving FDA approval under the brand name Glucophage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. Tanja, JJ., Langlass, TM.[2013]

Metformin is a first-line treatment for type 2 diabetes due to its effectiveness in reducing insulin resistance without causing weight gain or hypoglycemia, making it a safe option for patients.

Recent studies have shown that metformin also has cardiovascular benefits and may help in conditions beyond diabetes, such as insulin resistance and potentially tumor suppression, highlighting its broader therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin therapy and clinical uses. Scarpello, JH., Howlett, HC.[2022]

A retrospective chart review of 471 patients showed that those switched from immediate-release metformin to extended-release metformin (metformin-XR) experienced significantly fewer gastrointestinal side effects, including diarrhea, indicating better tolerability of the extended-release formulation.

The study found that while the overall frequency of gastrointestinal adverse events was similar between both formulations, patients who switched to metformin-XR reported a reduction in gastrointestinal issues, with diarrhea rates dropping from 18.05% to 8.29%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. Blonde, L., Dailey, GE., Jabbour, SA., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4200668/

Metformin in cancer prevention and therapy - PMC The results of numerous preclinical, epidemiological and clinical studies suggested that metformin use is associated with inhibition of cancer cell growth and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6497052/

The beneficial effects of metformin on cancer prevention ... Since 2005, metformin has been reported to reduce the risk of cancer by up to 23% worldwide. For example, the results of the Taiwan National Health Insurance ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05237960

Metformin for the Prevention of Oral Cancer in Patients ... This phase IIb trial tests whether metformin works in preventing oral cancer in patients with oral leukoplakia (white patches) or erythroplakia (red patches).

4. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04263-8

Metformin and cancer hallmarks: shedding new lights on ... Epidemiological evidence reveals that metformin reduces the risk of cancer and decreases cancer-related mortality in patients with diabetes; ...

5. aging-us.com aging-us.com/article/102787/text

Metformin: current clinical applications in nondiabetic ... In this review, we will present and discuss the latest findings regarding the potential anticancer role of metformin in nondiabetic patients with cancer.

6. aacrjournals.org aacrjournals.org/cancerpreventionresearch/article/13/2/195/258661/Metformin-Use-and-the-Risk-of-Cancer-in-Patients

Metformin Use and the Risk of Cancer in Patients with Diabetes This population-based cohort study showed that metformin therapy was not significantly associated with a lower risk of cancer among patients with diabetes. This ...