Metformin for Insulin Resistance in Breast Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: City of Hope Medical Center

Must not be taking: Oral antidiabetics, Tamoxifen

Disqualifiers: Diabetes, Renal insufficiency, Pregnancy, others

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

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: 30

Duration: 12 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding metformin, a common diabetes medication, to standard care can better prevent or reverse insulin resistance in women who have had stage I-III breast cancer and completed chemotherapy. Insulin resistance, where cells don't respond well to insulin, can lead to diabetes and heart issues and is linked to more aggressive breast cancer. Participants will receive either metformin with diet and exercise guidance or just the guidance alone. Women may qualify if they have completed treatment for stage I-III breast cancer within the last five years, are disease-free, and aren't already taking diabetes medications. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

You cannot participate in the trial if you are currently taking metformin or any other oral antidiabetic medications. However, you can continue taking weight loss medications like semaglutide during the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that metformin is generally safe for use. It is commonly prescribed for diabetes and has been studied for other conditions, such as certain types of cancer. For instance, one study found that metformin does not increase risks when combined with standard chemotherapy in women with advanced breast cancer, indicating its safety for these patients.

Another study found that women with HER2+ breast cancer who used metformin had a 48% lower risk of dying, suggesting that metformin might not only be safe but could also improve survival.

Overall, metformin is considered safe, particularly since it is already approved for diabetes treatment. Like any medication, it can have side effects, but they are usually manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Metformin is unique because, unlike traditional treatments for insulin resistance in breast cancer that primarily focus on diet, exercise, and hormone therapies, metformin acts directly on the body's metabolism. It lowers insulin resistance and improves glucose regulation, which could disrupt cancer cell growth. Researchers are excited because metformin's different mechanism could offer a new therapeutic avenue, potentially enhancing outcomes for patients by targeting the metabolic aspects of breast cancer.

What evidence suggests that metformin might be an effective treatment for insulin resistance in breast cancer?

Studies have shown that metformin can lower blood sugar by reducing the liver's sugar release and helping the body use sugar more effectively. Research also suggests that metformin may lower the risk of cancer and cancer-related deaths in people with diabetes. Some studies indicate that metformin might slow cancer cell growth by affecting various bodily processes. In this trial, one group of participants will receive metformin alongside standard care to explore its potential benefits for people with breast cancer, especially after chemotherapy. Although metformin primarily treats diabetes, researchers are actively studying its effects on breast cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Victoria L Seewaldt

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for women with stage I-III breast cancer who have completed chemotherapy and are at risk of developing insulin resistance, which can lead to diabetes and heart disease. Participants should not yet have type-2 diabetes but may be experiencing higher levels of insulin.

Inclusion Criteria

I finished my breast cancer treatment 30 days to 3 years ago and am now cancer-free.

My breast cancer is ER-negative and either HER2-normal or -high.

Documented informed consent of the participant and/or legally authorized representative

Exclusion Criteria

Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

I am currently taking medication for diabetes. I may also be taking medication for weight loss.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care healthy diet and exercise handouts and extended release metformin orally once daily for 12 months

12 months

Regular visits for blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up visits at 30 days and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview

The study is testing if taking metformin hydrochloride, along with standard diet and exercise education (usual care), is more effective than usual care alone in preventing or reversing insulin resistance after breast cancer treatment.

How Is the Trial Designed?

Group I: Arm I (standard of care, metformin) Experimental Treatment 4 Interventions

Patients receive standard of care healthy diet and exercise handouts and extended release metformin PO QD for 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

Group II: Arm II (standard of care) Active Control 3 Interventions

Patients receive standard of care healthy diet and exercise handouts on study. Additionally, patients undergo blood sample collection throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A meta-analysis of 11 studies involving 5,464 breast cancer patients with diabetes found that metformin significantly improves overall survival (HR: 0.53) and cancer-specific survival (HR: 0.89), suggesting it enhances the prognosis for these patients.

Subgroup analysis indicated that metformin improved overall survival by 65% when adjusted for hormone receptor expression, highlighting its potential role in standard cancer therapy for diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Use Is Associated With Better Survival of Breast Cancer Patients With Diabetes: A Meta-Analysis. Xu, H., Chen, K., Jia, X., et al.[2022]

In a study of 200 nondiabetic women with operable breast cancer, metformin did not significantly change the Ki-67 levels, a marker of tumor growth, compared to placebo after 4 weeks.

However, the effect of metformin varied based on insulin resistance, with a nonsignificant decrease in Ki-67 in women with higher insulin resistance (HOMA index > 2.8), suggesting that metabolic factors may influence the drug's potential antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial. Bonanni, B., Puntoni, M., Cazzaniga, M., et al.[2022]

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 141 women with type 2 diabetes who received chemotherapy for breast cancer, metformin use at diagnosis did not show any significant impact on recurrence-free survival (RFS), overall survival (OS), or the incidence of contralateral breast cancer (CBC) after a median follow-up of 87 months.

Despite observational data suggesting metformin may reduce breast cancer incidence in diabetic women, this analysis found no evidence that it improves cancer outcomes in those already diagnosed and undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of metformin on breast cancer outcomes in patients with type 2 diabetes. Oppong, BA., Pharmer, LA., Oskar, S., et al.[2022]

A systematic review of 10 randomized clinical trials involving 1520 breast cancer patients found that metformin therapy significantly reduced various health markers, including insulin levels and sex hormones, suggesting potential antitumor effects.

Despite these positive changes, metformin did not show a statistically significant improvement in overall survival or progression-free survival compared to control groups, indicating that more extensive clinical trials are needed to confirm its efficacy in breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of metformin on biomarkers and survivals for breast cancer- a systematic review and meta-analysis of randomized clinical trials. Zhang, ZJ., Yuan, J., Bi, Y., et al.[2019]

Metformin, a widely used and affordable medication for type 2 diabetes, shows promise as an anti-cancer agent, particularly in reducing the risk and mortality associated with breast cancer, supported by various preclinical and clinical studies.

The existing clinical experience with metformin allows for a faster evaluation process for its use in cancer treatment, as evidenced by the initiation of a Phase III adjuvant trial (NCIC MA.32) to further investigate its efficacy in breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents. Goodwin, PJ., Stambolic, V., Lemieux, J., et al.[2020]

Metformin, a diabetes medication, activates the AMPK pathway and inhibits cancer growth by reducing insulin levels and increasing insulin sensitivity, which is crucial since high insulin can promote cancer growth.

Preclinical studies show that metformin has anticancer effects across all breast cancer subtypes, suggesting it could be a promising treatment option for breast cancer in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin: a therapeutic opportunity in breast cancer. Gonzalez-Angulo, AM., Meric-Bernstam, F.[2018]

Metformin, a diabetes medication, may help lower breast cancer risk and improve outcomes by reducing insulin levels and directly affecting tumor cells through the activation of AMPK, which inhibits cancer growth pathways.

There is increasing evidence from various studies suggesting that metformin could be effective in preventing and treating breast cancer, with ongoing clinical trials exploring its use in different treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity and insulin resistance in breast cancer--chemoprevention strategies with a focus on metformin. Goodwin, PJ., Stambolic, V.[2022]

In a study of 32 women with early breast cancer, metformin significantly reduced fasting insulin levels by 22.4% and improved insulin sensitivity by 25.6%, suggesting potential benefits for breast cancer outcomes related to insulin levels.

The treatment also led to a modest weight loss of 2.5% and improved cholesterol levels, with minimal gastrointestinal side effects, indicating that metformin may be a safe and effective option for managing insulin levels in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin-lowering effects of metformin in women with early breast cancer. Goodwin, PJ., Pritchard, KI., Ennis, M., et al.[2022]

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