Clinical trial NCT02472353: Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer
Official title: A Phase II Pilot Study Using Metformin to Reduce Cardiac Toxicity in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Breast Tumors
Keywords: breast
cancer
doxorubicin
metformin
cardiotoxicity
ejection fraction
LVEF
Lead sponsor: Avera McKennan Hospital & University Health Center
Sponsor class: OTHER
First posted: 2015-06-15
Enrollment: 30
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
Study officials:
affiliation: Avera McKennan Hospital & University Health Center
name: Kirstin Williams, CNP
role: PRINCIPAL_INVESTIGATOR
References: