Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer

Study Overview
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Brief Summary
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The goal of this study is to determine if co-administration of metformin and doxorubicin in breast cancer patients receiving neoadjuvant or adjuvant therapy will reduce the number of patients who develop a significant change in left ventricle ejection fraction (LVEF).

Detailed Description
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This is a randomized, open-label, phase II design pilot study in patients with breast cancer requiring neoadjuvant or adjuvant chemotherapy. Eligible patients will be equally randomized to either receive metformin plus standard of care therapy or standard of care therapy alone. Patients receiving metformin will continue drug until the doxorubicin-containing cycles are complete, unless unacceptable toxicity occurs or the patient decides to withdraw from the study. Both arms of the study will undergo echocardiograms with contrast at baseline, upon completion of doxorubicin-containing cycles (within 28 days of completion), and at the one-year and seven-year time points. Additionally biomarker labs will be obtained to explore if there is a correlation between change in cardiac activity and the activity of metformin. If willing, all enrolled patients will provide a sample of whole blood for further exploratory analysis. Symptoms reported during the study will be correlated with know single nucleotide polymorphisms (SNPs) found during an exploratory genomic analysis.

Official Title
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A Phase II Pilot Study Using Metformin to Reduce Cardiac Toxicity in Breast Cancer Patients

Conditions
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Breast Cancer, Breast Tumors

Intervention / Treatment
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* Drug: Metformin
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Breast cancer requiring neoadjuvant or adjuvant therapy with doxorubicin Complete metabolic panel demonstrating adequate organ functions as defined by the following: Aspartate transaminase (AST) less than 2.5 times Upper Limit of Normal (ULN); Alanine transaminase (ALT) less than 2.5 times ULN; alkaline phosphatase less than 2.5 times ULN; serum creatinine less than 1.5 mg/dL; serum bilirubin less than ULN Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Age greater than or equal to 21 years Exclusion Criteria: Known diabetes History of cardiac arrhythmias or symptomatic cardiac disease Currently taking antiarrhythmic medications, beta-blockers, or other rate controlling cardiac medications Currently taking metformin and/or sulfonylureas Known hypersensitivity or intolerance to metformin Baseline ejection fraction of less than 50% measured by echocardiogram Known hypersensitivity to contrast used during echocardiogram Risk factors associated with increased risk of metformin-associated lactic acidosis (e.g. congestive heard failure, history of acidosis, habitual intake of 3 or more alcoholic beverages per day) Pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin. | Drug: Doxorubicin<br>* Standard of care treatment with doxorubicin<br>|
| Experimental: Metformin + Standard of Care<br>Patients will receive metformin during their treatment with doxorubicin for their breast cancer. | Drug: Metformin<br>* Metformin will begin to be administered prior to treatment with doxorubicin. Metformin will continue to be given throughout doxorubicin cycles until the completion of doxorubicin therapy.<br>* Other names: Glucophage;Drug: Doxorubicin<br>* Standard of care treatment with doxorubicin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram | Determine whether the addition of metformin to standard doxorubicin therapy in breast cancer patients will decrease the incidence of change in left ventricle ejection fraction (LVEF). | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast, cancer, doxorubicin, metformin, cardiotoxicity, ejection fraction, LVEF