Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer

NCT ID: NCT02472353

Last Updated: 2019-10-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2018-05-23

Brief 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).

Detailed 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.

Conditions

Breast Cancer; Breast Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Standard of Care

Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin.

Group Type: ACTIVE_COMPARATOR

Doxorubicin

Intervention Type: DRUG

Standard of care treatment with doxorubicin

Metformin + Standard of Care

Patients will receive metformin during their treatment with doxorubicin for their breast cancer.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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

Intervention Type: DRUG

Standard of care treatment with doxorubicin

Interventions

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.

Intervention Type: DRUG

Doxorubicin

Standard of care treatment with doxorubicin

Intervention Type: DRUG

Other Intervention Names

Glucophage

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Avera McKennan Hospital & University Health Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kirstin Williams, CNP

Role: PRINCIPAL_INVESTIGATOR

Avera McKennan Hospital & University Health Center

Locations

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Countries

United States

References

Sun ML, Dong JM, Liu C, Li P, Zhang C, Zhen J, Chen W. Metformin-mediated protection against doxorubicin-induced cardiotoxicity. Biomed Pharmacother. 2024 Nov;180:117535. doi: 10.1016/j.biopha.2024.117535. Epub 2024 Oct 15.

Reference Type: DERIVED

PMID: 39405911 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AMEM-2014-MET001

Identifier Type: -

Identifier Source: org_study_id