Imaging Versus Cardiac Biomarker Monitored HER2 Directed Therapy in Patients With Breast Cancer

Not Applicable

Recruiting

• Conditions: Cardiotoxicity; HER2-positive Breast Cancer

• Registration Number: NCT05406635
• Lead Sponsor: Odense University Hospital

Brief Summary

Due to a risk of heart failure during HER2 directed therapy in breast cancer, treatment is monitored with imaging of myocardial function, which is resource demanding for both patients and the health care system. The purpose of this study is to evaluate, if biomarkers can replace imaging based examinations of myocardial function during HER2 directed therapy.

Detailed Description

About 15% of breast cancer tumors express the Human Epidermal Growth Factor Receptor 2 (HER2), which is associated with a poor prognosis. Antibodies (trastuzumab and pertuzumab) directed against HER2 have in addition to traditional chemotherapy significantly improved survival in HER2 positive breast cancer, but induce a risk of left ventricular dysfunction and heart failure. Regular imaging based evaluation of myocardial function is therefore recommended during HER2 directed therapy by either an echocardiography or a MUGA scan, which is associated with radiation exposure. Both types of scans are resources demanding for both patients and the healthcare system, and since biomarkers have been proposed as another modality in assessment of myocardial injury, the purpose of this study is to evaluate, if biomarkers can replace imaging based examinations of myocardial function during HER2 directed therapy.

The study is designed as a national multicenter, randomized study, which will include Odense University Hospital, Herlev and Gentofte University Hospital and Aarhus University Hospital. It will be possible to include more sites.

Patients with localized HER2-positive breast cancer scheduled for HER2 proper therapy will be randomized 1: 1 to:

1. Standard imaging monitored treatment as recommended by DBCG guidelines with measurement of LVEF by MUGA scan or echocardiography in weeks 0, 9, 18, 30 and 48 of the treatment period. At each control visit, biomarkers are also taken, which are blinded until the end of the study.

2. Biomarker monitored treatment with measurement of NT-proBNP and cTNT / TNI in weeks 0, 9, 18, 30 and 48 of the treatment period. At each of these follow-up visits, MUGA scans or echocardiography are also performed, but the results are blinded to the staff responsible for treatment decisions.

In the group followed by standard imaging monitoring, cardiotoxicity will be managed according to standard clinical guidelines. Cardiotoxicity in the biomarker group will be suspected in case of a doubling of NT-proBNP from baseline (but minimum 125 pg / ml) and / or an increase in troponins to above 99th percentile. If these criteria are met, imaging is triggered, which in practice is a blinding of the result of the examination already performed.

The primary endpoint of the study is LVEF measured by cardiac MRI scan three months after completion of HER2-directed therapy.

Study Timeline

• Study Start: 2021-10-01
• Study First Submitted: 2022-05-12
• Study First Submitted QC: 2022-06-03
• Study First Posted: 2022-06-06
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-30
• Last Update Posted: 2023-12-01
• Primary Completion: 2024-12-01
• Study Completion: 2025-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 220

Inclusion Criteria

• Patients with non-metastatic HER2 positive breast cancer
• Scheduled for standard chemotherapy and HER2 directed therapy with trastuzumab +/- pertuzumab
• Age > 18 years
• Sinus rhythm on ECG
• NT-proBNP below125 pg/ml
• Troponin below threshold limit value
• LVEF > 55% by MUGA scan or an echocardiogram

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Exclusion Criteria

• Contra indications for cardiac magnetic resonance imaging (CMRI)
• Chronic obstructive pulmonary disease with FEV1 <80 % of predicted

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Left ventricular ejection fraction (LVEF)	Three months after treatment has ended.	LVEF on cardiac MR.

Secondary Outcome Measures

Name	Time	Method
The number of MUGA scans/echocardiograms	Through study completion, an average of 1 year.	The number of MUGA scans/echocardiograms preformed during the study periode.
The number of treatment interruptions due to suspected cardiotoxicity	Through study completion, an average of 1 year.	Number of times treatment was paused due to suspected cardiotoxicity either based on imaging or biomarkes as defined in the protocol.
The cumulative doses of trastuzumab and pertuzumab	After end of treatment, an average of 1 year after inclusion.	The cumulative doses of trastuzumab and pertuzumab in mg.
The proportion of patients treated for cardiotoxicity.	Through study completion, an average of 1 year	Number of patients referred to tratment for heart failure in the department of cardiology.
Change in self-reported health status measured with EQ-5D-5L questionnaire	At baseline, at treatment week 9, 18, 30 and 48 and three months after end of treatment.	An Index score and a Visual Analogue Scale (VAS).
Correlation between radiotherapy and cardiac function.	Through study completion, an average of 1 year	Correlation between location and dose of the radiotherapy with changes in biomarkers, LVEF and ECG.

Trial Locations

Locations (4)

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

Herlev University Hospital; 🇩🇰 Herlev, Denmark