Metformin for Breast Cancer Prevention

Recruiting at 27 trial locations

Overseen By Victoria Seewaldt, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Warfarin, Tamoxifen, Raloxifene, others

Disqualifiers: Active malignancy, BMI < 25, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 36

Duration: 12 months

86 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking tamoxifen, raloxifene, warfarin, or certain other medications like pyrimethamine, cimetidine, rifampin, or cephalexin. If you are taking metformin, you must not have taken it in the past 90 days.

What evidence supports the effectiveness of the drug Metformin for breast cancer prevention?

Research suggests that Metformin, commonly used for type 2 diabetes, may lower the risk of breast cancer and improve survival rates in patients with breast cancer, as indicated by a meta-analysis and studies on its anticancer properties. ^{1 2 3 4 5}

Is Metformin generally safe for humans?

Metformin has been used safely for many years to treat type 2 diabetes, with common side effects including stomach issues like diarrhea and nausea, and a decrease in vitamin B12 absorption. It is considered safe and has a good track record for cardiovascular safety. ^{6 7 8 9 10}

How does the drug Metformin differ from other treatments for breast cancer prevention?

Metformin, commonly used for type 2 diabetes, is being studied for breast cancer prevention due to its potential to lower cancer risk and improve prognosis. Unlike traditional cancer treatments, Metformin is known for its safety, affordability, and ability to control blood sugar, which may contribute to its anti-cancer effects. ^{1 11 12 13 14}

What is the purpose of this trial?

This randomized phase III trial studies metformin hydrochloride to see how well it works compared to placebo in preventing breast cancer in patients with atypical hyperplasia or in situ breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of metformin hydrochloride may prevent breast cancer.

Research Team

Victoria Seewaldt, MD

Principal Investigator

City of Hope Comprehensive Cancer Center

Eligibility Criteria

This trial is for women at high risk for breast cancer due to factors like a history of certain breast conditions, a strong family history of breast or ovarian cancer, or known BRCA1/2 mutations. Participants must have normal blood counts and organ function, not be pregnant or breastfeeding, and willing to use birth control if menstruating. They should not have had metformin recently, no other active cancers (with some exceptions), and cannot be on specific medications like Warfarin.

Inclusion Criteria

Willing to provide RPFNA and blood samples for correlative research purposes

I am eligible for tamoxifen but have chosen not to take it.

Your AST blood test result is not more than three times the upper limit of normal.

Exclusion Criteria

Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

You are currently diagnosed with alcoholism.

I have taken metformin in the last 90 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin hydrochloride or placebo for 12 months

12 months

Monthly visits (in-person)

Crossover/Extension

Participants on placebo may crossover to metformin for an additional 12 months

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Follow-up visits at 36 and 48 months

Treatment Details

Interventions

• Metformin Hydrochloride
• Placebo

Trial Overview The study is testing whether metformin hydrochloride can prevent the development of breast cancer in patients with atypical hyperplasia or in situ breast cancer compared to a placebo. It's a phase III trial where participants are randomly assigned to either the drug group or the placebo group.

Participant Groups

Group I: Arm I: metformin hydrochloride Experimental Treatment 1 Intervention

Patients receive metformin hydrochloride PO QD or BID for 24 months. Patients will continue metformin 850 mg PO BID for months 13-24. Patients will undergo RPFNA at 24 months. Follow up visits will be performed at 36 and 48 months after the start of treatment.

Group II: Arm II: placebo Placebo Group 1 Intervention

Patients receive placebo PO QD or BID for 12 months. Patients may crossover to Arm I for months 13-24.

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?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A meta-analysis of 15 studies involving 838,333 participants found that metformin use does not significantly reduce the incidence of breast cancer among patients with type 2 diabetes (RR, 0.964).

However, metformin therapy is associated with a significant decrease in all-cause mortality (RR, 0.652), suggesting it may improve survival rates in patients affected by breast cancer, although further research is needed to confirm this finding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Metformin Therapy and Breast Cancer Incidence and Mortality: Evidence from a Meta-Analysis. Yang, T., Yang, Y., Liu, S.[2020]

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]

In a study involving 24 healthy male volunteers, the bioavailability of two metformin tablet formulations was compared, showing that both formulations had equivalent absorption when taken after fasting.

Key pharmacokinetic parameters, such as maximum concentration and area under the curve, were similar for both formulations, indicating that they can be considered equivalent in their effectiveness for delivering metformin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence study of two metformin formulations. Al Hawari, S., AlGaai, E., Yusuf, A., et al.[2013]

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 126 overweight and obese patients with type 2 diabetes, dulaglutide (DU) showed a significant and sustained reduction in HbA1c levels over 18 months, with a mean decrease of -0.85% at 6 months, indicating its effectiveness as an add-on therapy to metformin.

Dulaglutide was associated with a higher percentage of patients achieving glycemic targets (HbA1c ≤ 7.0%) compared to liraglutide (LIRA) at 18 months, with 64.8% of DU patients reaching this target versus 42.6% for LIRA, highlighting its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes. Mirabelli, M., Chiefari, E., Tocci, V., et al.[2021]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Association between Metformin Therapy and Breast Cancer Incidence and Mortality: Evidence from a Meta-Analysis. [2020]

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

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

3. Thailand pubmed.ncbi.nlm.nih.gov

The Effect of Metformin on Survival Outcomes of Non-Metastatic Breast Cancer Patients with Type 2 Diabetes. [2021]

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

In vitro metformin anti-neoplastic activity in epithelial ovarian cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Glycaemic efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors as add-on therapy to metformin in subjects with type 2 diabetes-a review and meta analysis. [2022]

6. 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]

7. Germany pubmed.ncbi.nlm.nih.gov

Bioequivalence study of two metformin formulations. [2013]

8. 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]

9. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Efficacy and Cardiovascular Safety of Metformin. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Effectiveness and Safety of Once-Weekly GLP-1 Receptor Agonist Dulaglutide as Add-On to Metformin or Metformin Plus Insulin Secretagogues in Obesity and Type 2 Diabetes. [2021]

11. Canada pubmed.ncbi.nlm.nih.gov

The Effect of Metformin on the Clinicopathological Features of Breast Cancer With Type 2 Diabetes. [2022]

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

Metformin, an old drug, brings a new era to cancer therapy. [2018]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Metformin intervention in obese non-diabetic patients with breast cancer: phase II randomized, double-blind, placebo-controlled trial. [2015]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer. [2020]