Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02472353
• Other study ID #: AMEM-2014-MET001
• Status: Terminated
• Phase: Phase 2
• Start date: July 2014
• Est. completion date: May 23, 2018

Study information

• Verified date: September 2019
• Source: Avera McKennan Hospital & University Health Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: May 23, 2018
• Est. primary completion date: May 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Breast Tumors
• Cardiotoxicity

Intervention

Drug:
• Metformin
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.
• Doxorubicin
Standard of care treatment with doxorubicin

Locations

Country	Name	City	State
United States	Avera Cancer Institute	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Avera McKennan Hospital & University Health Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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