Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer

NCT02472353 | Terminated Phase 2 Results DMC

• 1 other identifier: AMEM-2014-MET001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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).

Conditions

Breast Cancer; Breast Tumors

Keywords

breast; cancer; doxorubicin; metformin; cardiotoxicity; ejection fraction; LVEF

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

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

Drug: Doxorubicin

Metformin + Standard of Care

EXPERIMENTAL

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

Drug: Metformin; Drug: Doxorubicin

Interventions

Metformin 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.

Also known as: Glucophage

Metformin + Standard of Care

Doxorubicin DRUG

Standard of care treatment with doxorubicin

Metformin + Standard of Care; Standard of Care

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Avera McKennan Hospital & University Health Center: lead

Study Sites (1)

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Related Publications (1)

• 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.

  PMID: 39405911 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms; Cardiotoxicity

Interventions

Metformin; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Limitations and Caveats

The study was terminated early due to slow accrual.

Results Point of Contact

• Title: Stacy Kehoe
• Organization: Avera

Stacy.Kehoe@avera.org

605.322.3082

Study Officials

• Kirstin Williams, CNP

  Avera McKennan Hospital & University Health Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2015
• First Posted: June 15, 2015
• Study Start: July 1, 2014
• Primary Completion: May 23, 2018
• Study Completion: May 23, 2018
• Last Updated: October 16, 2019
• Results First Posted: October 16, 2019

Record last verified: 2019-09

Locations

US (1)