Strain vs. Left Ventricular Ejection Fraction-based Cardiotoxicity Prevention in Breast Cancer

Strain-based vs. Left Ventricular Ejection Fraction-based Cardiotoxicity Prevention Strategy in Patients With Breast Cancer Who Treated With Adjuvant Trastuzumab

Comparing preventive effect of myocardial global longitudinal strain-based cardioprotective stragety (angiotensin receptor blocker prophylaxis) with left ventricular ejection fraction-based strategy in breast cancer patients treated with adjuvant trastuzumab.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Cardiotoxicity; Prevention; Adjuvant; Trastuzumab
• Intervention / Treatment: Drug: Candesartan

Detailed Description

Despite the left ventricular global longitudinal strain (GLS) enables early prediction of trastuzumab-related cardiomyopathy, its clinical application has been hampered due to the lack of appropriate evaluation and treatment strategies. Therefore, we aimed to evaluate the effect of early intervention strategy (GLS-based cardiotoxicity monitoring and administration of candesartan) by comparing with conventional intervention strategy (left ventricular ejection fraction-based cardiotoxicity monitoring and administration of candesartan) in breast cancer patients who treated with adjuvant trastuzumab.

• Study Type: Interventional
• Enrollment (Anticipated): 136
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yeon Hee Park, MD, PhD; Phone Number: +82-2-3410-3450; Email: yeonh.park@samsung.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
    • Contact: Yeon Hee Park, MD, Ph.D; Phone Number: +82-2-3410-3459; Email: yeonh.park@samsung.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female aged ≥ 18 years
• Pathologically confirmed HER2-positive breast cancer
• Adjuvant treatment plan comprises at least 12 cycles of Trastuzumab
• Baseline echocardiogram should be performed before starting trastuzumab
• Cumulative anthracycline dose ≤ 300mg/m2
• Written informed consent to participate in the study

Exclusion Criteria:

• History of hypersensitivity or alllergic reaction to the study medication
• Metastatic breast cancer
• Treatment with angiotensin converting enzyme(ACE) inhibitor , Angiotensin receptor blocker (ARB), beta-blocking agents, or diuretics
• Patients with NCI/CTCAE grade ≥ 2 congestive heart failure, myocardial infarction, symptomatic left ventricular systolic dysfunction, heart's valve disease (≥ moderate), arrhythmias (Grade ≥ 3) < 12 months before enrollment
• Pregnancy or breast feeding
• Baseline systolic pressure < 90mmHg
• Cumulative anthracycline dose > 300mg/m2
• Serious concurrent illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional Cardiac intervention; Starting candesartan in patients with left ventricular ejection fraction (LVEF) between 45% and 50% by echocardiogram.	Drug: Candesartan; If GLS decreased less than 18% or LVEF decreased to 45-50% during the treatment of adjuvant trastuzumab, start candesartan medication.
Active Comparator: Early Cardiac intervention; Starting candesartan in patients with decreased myocardial strain below 18% regardless of LVEF by echocardiogram.	Drug: Candesartan; If GLS decreased less than 18% or LVEF decreased to 45-50% during the treatment of adjuvant trastuzumab, start candesartan medication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular ejection fraction (LVEF)	Maximum change in LVEF	at months 3,6,9,12,18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overt chemotherapy induced cardiotoxicity	LVEF < 45%, decline in LVEF by >10% to a value to 45-49%, symptomatic congestive heart failure	any time
Changes in cardiac biomarker	NT-pro BNP, cardiac troponin	at months 3,6,9,12,18

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2019
• Primary Completion (Anticipated): July 18, 2022
• Study Completion (Anticipated): July 18, 2023

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Actual): June 12, 2020
• Last Update Submitted That Met QC Criteria: June 10, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Breast Neoplasms; Cardiotoxicity; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Candesartan
• Other Study ID Numbers: 2018-11-128

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No