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

HER2-positive Breast Cancer Clinical Trial

— HER2BIC  

Official title:

A National Randomized Non-inferiority Trial: Imaging Versus Cardiac Biomarker Monitored HER2 Directed Therapy in Patients With Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05406635
• Other study ID #: OP_1413
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2021
• Est. completion date: September 1, 2025

Study information

• Verified date: November 2023
• Source: Odense University Hospital
• Contact: Ann Banke, MD, PHD
• Phone: +4526278303
• Email: Ann.Banke[@]rsyd.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: September 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Cardiotoxicity
• HER2-positive Breast Cancer

Intervention

Diagnostic Test:
• Biomarkers: Troponins and natriuretic peptides
Biomarker monitored treatment with measurement of NT-proBNP and cTNT / TNI in weeks 0, 9, 18, 30 and 48 of the treatment period.

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev University Hospital	Herlev
Denmark	Odense University Hospital	Odense

Sponsors (4)

Lead Sponsor	Collaborator
Odense University Hospital	Aalborg University Hospital, Aarhus University Hospital, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safty outcome of left ventricular ejection fraction	Drop in LVEF below 45 %	End of treatment
Primary	Left ventricular ejection fraction (LVEF)	LVEF on cardiac MR.	Three months after treatment has ended.
Secondary	The number of treatment interruptions due to suspected cardiotoxicity	Number of times treatment was paused due to suspected cardiotoxicity either based on imaging or biomarkes as defined in the protocol.	Through study completion, an average of 1 year.
Secondary	The number of MUGA scans/echocardiograms	The number of MUGA scans/echocardiograms preformed during the study periode.	Through study completion, an average of 1 year.
Secondary	The cumulative doses of trastuzumab and pertuzumab	The cumulative doses of trastuzumab and pertuzumab in mg.	After end of treatment, an average of 1 year after inclusion.
Secondary	The proportion of patients treated for cardiotoxicity.	Number of patients referred to tratment for heart failure in the department of cardiology.	Through study completion, an average of 1 year
Secondary	Change in self-reported health status measured with EQ-5D-5L questionnaire	An Index score and a Visual Analogue Scale (VAS).	At baseline, at treatment week 9, 18, 30 and 48 and three months after end of treatment.
Secondary	Correlation between radiotherapy and cardiac function.	Correlation between location and dose of the radiotherapy with changes in biomarkers, LVEF and ECG.	Through study completion, an average of 1 year

External Links

•   Link to study description af Open Patient data Explorative Network