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

April 4, 2025 updated by: Ann Banke, Odense University Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

220

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Denmark
      • Aalborg, Denmark, 9000
        • Recruiting
        • Aalborg University Hospital
        • Contact:
      • Copenhagen, Denmark
      • Herlev, Denmark
      • Odense, Denmark, 5000
        • Recruiting
        • Odense University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard imaging monitored treatment
Standard care + biomarkers, which are blinded until end of study.
Experimental: Intervention biomarker monitored treatment
biomarker monitored treatment + imaging, which is blinded until end of study
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Left ventricular ejection fraction (LVEF)
Time Frame: Three months after treatment has ended.
LVEF on cardiac MR.
Three months after treatment has ended.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of treatment interruptions due to suspected cardiotoxicity
Time Frame: 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.
Through study completion, an average of 1 year.
The number of MUGA scans/echocardiograms
Time Frame: Through study completion, an average of 1 year.
The number of MUGA scans/echocardiograms preformed during the study periode.
Through study completion, an average of 1 year.
The cumulative doses of trastuzumab and pertuzumab
Time Frame: After end of treatment, an average of 1 year after inclusion.
The cumulative doses of trastuzumab and pertuzumab in mg.
After end of treatment, an average of 1 year after inclusion.
The proportion of patients treated for cardiotoxicity.
Time Frame: Through study completion, an average of 1 year
Number of patients referred to tratment for heart failure in the department of cardiology.
Through study completion, an average of 1 year
Change in self-reported health status measured with EQ-5D-5L questionnaire
Time Frame: 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).
At baseline, at treatment week 9, 18, 30 and 48 and three months after end of treatment.
Correlation between radiotherapy and cardiac function.
Time Frame: Through study completion, an average of 1 year
Correlation between location and dose of the radiotherapy with changes in biomarkers, LVEF and ECG.
Through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safty outcome of left ventricular ejection fraction
Time Frame: End of treatment
Drop in LVEF below 45 %
End of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Odense University Hospital

Collaborators

Aarhus University Hospital
University of Copenhagen
Aalborg University Hospital

Investigators

  • Principal Investigator: Ann Banke, MD PHD, Odense Universitetshospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2021

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

May 12, 2022

First Submitted That Met QC Criteria

June 3, 2022

First Posted (Actual)

June 6, 2022

Study Record Updates

Last Update Posted (Actual)

April 8, 2025

Last Update Submitted That Met QC Criteria

April 4, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OP_1413

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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