Metformin for Breast Cancer Prevention

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if metformin, a common diabetes medication, can help prevent breast cancer in women at higher risk. Participants will receive either metformin or a placebo to compare outcomes. Women with certain breast cell changes (such as atypical hyperplasia or specific early-stage cancers), a strong family history of breast or ovarian cancer, or BRCA gene mutations may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that metformin hydrochloride is generally safe for use. Studies have found that people with diabetes who take metformin have a lower risk of developing cancer, including breast cancer, suggesting it might be safe for long-term use.

Metformin has already received FDA approval for treating diabetes, indicating it has passed many safety tests. Although this trial explores a new use for metformin, its existing approval provides some confidence in its safety.

In earlier studies, some people taking metformin experienced mild side effects like an upset stomach. These side effects are usually not serious and often resolve over time. There is no strong evidence of serious side effects related to metformin when used for cancer prevention. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for breast cancer, which often include surgery, chemotherapy, and hormone therapy, metformin is traditionally a diabetes medication. Researchers are excited about metformin because it might prevent breast cancer by reducing insulin levels and inflammation, which are linked to cancer growth. This repurposing of an existing drug could offer a new, non-invasive option for cancer prevention, making it an attractive prospect for expanding the arsenal against breast cancer.

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

This trial will compare metformin hydrochloride with a placebo to evaluate its potential in breast cancer prevention. Studies have shown that metformin might help lower the risk of breast cancer. In women with breast cancer, metformin has been linked to fewer cancer cells. Additionally, people with diabetes who take metformin appear to have a lower risk of cancer. This suggests that metformin might help prevent cancer, including breast cancer. Furthermore, the drug is considered safe and affordable, making it a possible option for breast cancer prevention. ^{1 5 6 7 8}

Who Is on the Research Team?

Victoria Seewaldt, MD

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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