Comparison of two care schedules for monitoring of cardiotoxicity in patients receiving trastuzumab-based therapy for early-stage breast cancer: study protocol for a randomized controlled non-inferiority trial

Abstract

Background: Cardiotoxicity is a toxic side effect of trastuzumab-based therapy. Current guidelines for cardiac monitoring (every 3 months) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving trastuzumab-based therapy have been dictated by the increased risk of cardiotoxicity observed in clinical trials. However, the majority of these patients are at a low risk of cardiac complications and may not require such frequent monitoring. Objective: This randomized controlled clinical trial will be performed to demonstrate that cardiac monitoring (echocardiography (ECHO)/multiple gated acquisition scan (MUGA) every 4 months is not inferior to every 3 months in the detection of cardiac dysfunction (decrease in left ventricular ejection fraction (LVEF)) in patients receiving trastuzumab-based therapy for early-stage HER2-positive breast cancer. Study period: From June 2016 to December 2018. Study location: The Ottawa Hospital Cancer Centre. Principal investigator: Dr. Olexiy Aseyev and Dr. Susan Dent at Department of Medicine, Division of Medical Oncology, The Ottawa Hospital, University of Ottawa, Canada. Study design: A prospective, single-center, randomized controlled non-inferiority clinical trial. Study population: A total of 200 patients with early-stage HER2-positive breast cancer (n = 100 in each group) receiving trastuzumab-based therapy will be enrolled. Inclusion criteria: Patients with histologically confirmed early-stage HER2-positive breast cancer receiving trastuzumab-based therapy, who are over 18 years of age, have a normal baseline LVEF (> 53%) and are able to provide verbal consent will be included in this study. Exclusion criteria: Patients will be excluded if they have any contraindication to transthoracic echocardiography or MUGA. Randomization: Eligible and consented patients will be randomized using a permuted block design to receive cardiac evaluation (by either transthoracic echocardiography or MUGA) every 3 months, or every 4 months while on treatment, 100 patients for each type of cardiac evaluation. Primary outcome measure: The rate of changes in LVEF diagnosed by ECHO or MUGA throughout trastuzumab-based therapy in both groups. Secondary outcome measures: Rates of trastuzumab delay/discontinuation, referral to cardiology, rate of cardiac events. Human specimen collection: Not involved. Ethical approval: This study was approved by the Ottawa Health Science Network Research Ethics Board. Trial registration: ClinicalTrials.gov identifier: NCT02696707 on February 18, 2016. Study status: This study is currently recruiting participants. Study enrolment is expected to be completed by July 2018 and analysis of primary outcome measure will be completed by October 2018 and the study will be completed by December 2018. Discussion: This study will present data on the cardiac safety of less frequent cardiac monitoring in patients with early-stage HER2-positive breast cancer. Future trials will explore cardiac monitoring strategies using composite data including baseline cardiac risk factors, baseline cardiac imaging and cardiac biomarkers. Health care economics will be explored.