did not meet target accrual

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).

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.

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

Time point 1: Within 2 weeks of starting metformin Time point 2: 4 weeks after starting metformin Time point 3: 7 weeks after starting metformin Time point 4: 9 weeks after starting metformin (last assessment during treatment period)

The study was terminated early due to slow accrual.