Imaging Versus Cardiac Biomarker Monitored HER2 Directed Therapy in Patients With Breast Cancer (HER2BIC)

Odense University Hospital

Status: Enrolling

Conditions: Cardiotoxicity; HER2-positive Breast Cancer

Treatments: Diagnostic Test: Biomarkers: Troponins and natriuretic peptides

Study type: Interventional

Funder types: Other

Identifiers

NCT05406635

OP_1413

Details and patient eligibility

About

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.

Full 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.

Enrollment: 220 estimated patients

Sex: Female

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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220 participants in 2 patient groups

Standard imaging monitored treatment

No Intervention group

Description:

Standard care + biomarkers, which are blinded until end of study.

Intervention biomarker monitored treatment

Experimental group

Description:

biomarker monitored treatment + imaging, which is blinded until end of study

Treatment:

Diagnostic Test: Biomarkers: Troponins and natriuretic peptides