Metformin for Preventing Oral Cancer

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

26 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of the drug Metformin in preventing oral cancer?

Research suggests that Metformin, commonly used for type 2 diabetes, might help prevent the progression of oral lesions to cancer, as seen in lab and animal studies. However, the evidence in humans is mixed, with some studies indicating potential benefits in head and neck cancer patients, especially those with diabetes. ^{1 2 3 4 5}

Is Metformin safe for humans?

Metformin is generally considered safe for humans when used as directed, with common side effects being gastrointestinal issues like diarrhea and nausea. It is important to monitor kidney function, as serious side effects like lactic acidosis are rare but possible, especially in those with impaired renal function. ^{6 7 8 9 10}

How is the drug metformin unique in preventing oral cancer?

Metformin, commonly used to treat type 2 diabetes, is being studied for its potential to prevent oral cancer by stopping the progression of pre-cancerous lesions. This is unique because it targets cancer prevention rather than treatment, and its effectiveness in this role is still being explored. ^{1 4 11 12 13}

What is the purpose of this trial?

This trial tests if metformin hydrochloride can prevent oral cancer in patients with specific mouth lesions. These lesions can increase cancer risk, and metformin may help by slowing cell growth and affecting proteins related to cancer development. Metformin, widely used as a diabetes medication, has recently been reported to reduce cancer risk and improve outcomes in certain cancers.

Research Team

Scott M Lippman

Principal Investigator

The University of Arizona Medical Center-University Campus

Eligibility Criteria

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

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Metformin Prevents the Progression of Dysplastic Mucosa of the Head and Neck to Carcinoma in Nondiabetic Patients. [2019]

2. Slovakia pubmed.ncbi.nlm.nih.gov

Implications of diabetes in head and neck cancer - A single center real-world data. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Impact of metformin on disease control and survival in patients with head and neck cancer: a retrospective cohort study. [2020]

4. Thailand pubmed.ncbi.nlm.nih.gov

Association of Diabetes with Oral Cancer- an Enigmatic Correlation. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

What every dentist should know about metformin, diabetes, and cancer. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Metformin therapy and clinical uses. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Metformin hydrochloride: an antihyperglycemic agent. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. [2021]

10. France 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]. [2023]

11. Ukraine pubmed.ncbi.nlm.nih.gov

Cytotoxic activity of metformin in vitro does not correlate with its antitumor action in vivo. [2018]

12. Poland pubmed.ncbi.nlm.nih.gov

Metformin and proliferation of cancer cell lines. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

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