NT-proBNP to Assess Trastuzumab-induced Cardiotoxicity

March 29, 2024 updated by: Vastra Gotaland Region

Monitoring Heart Function Through Blood Test Analysis of NT-proBNP During Treatment With HER2-Targeted Antibodies in HER2-Positive Breast Cancer - A Swedish Multicenter Study

Trastuzumab-induced cardiotoxicity (TIC) will be monitored in patients with HER2+ breast cancer undergoing trastuzumab treatment before and after breast cancer surgery. At baseline before start of trastuzumab treatment, echocardiography (ECHO)/multigated Acquisition Scan (MUGA) and measurement of plasma NT-proBNP will be performed. NT-proBNP will be measured again at 6 months and at 12 months of trastuzumab treatment. If elevations in NT-proBNP at 6 months and 12 months occur patients will be referred for ECHO/MUGA. The aim is to assess the sensitivity and specificity to detect TIC with NT-proBNP and whether ECHO/MUGA can be safely replaced by assessment of plasma NT-proBNP levels.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Sponsor: Swedish Association of Breast Oncologists (SABO), Clinical Trial Unit, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.

Design:This is an national multicentre single arm phase II trial for patients with primary HER2 positive breast cancer planned for neoadjuvant/adjuvant treatment with HER2 blocking agents.

Purpose: The purpose of this study is to assess the sensitivity and specificity of NT-proBNP for detection of cardiac failure in patients with primary breast cancer that receive neoadjuvant/adjuvant treatment with HER2 blocking compounds.

Background: Patients with HER2 positive breast cancer > 20 mm and/or with lymph node metastasis receive, according to the national guidelines 4 courses of double antibody blockade with trastuzumab and pertuzumab plus a taxane for 12 weeks followed by EC (epirubicin/cyclophosphamide) every 3rd week times 3 in the neoadjuvant setting followed by continued HER2 blockade with trastuzumab or TDM-1 for a total of 17 courses. Patients with tumours < 20 mm and node-negative disease start with surgery followed by adjuvant treatment with EC x 4 followed by trastuzumab and a taxane for 12 weeks, thereafter trastuzumab x 13 is given as a single agent. For patients with tumours < 10 mm and node negative it is considered sufficient to give only a taxane plus trastuzumab for 12 weeks followed by trastuzumab times 13. The latter less toxic regimen has also been used in elderly fragile patients.

The risk of cardiac dysfunction as determined by a reduction in the Left Ventricular Ejection Fraction (LVEF) below 50% has been estimated to approximately 3-4% in the large registration trials.

Cardiac function is followed by repeated echocardiography (ECHO)/ Multigated Acquisition Scan (MUGA) that are performed before start of HER2 blocking treatment, after 6 and 12 months (when the treatment is completed.

Because cardiac toxicity is very low, a labour-intensive method needs to be carried out unnecessarily on a large number of patients. We have shown in a single centre pilot study of 136 patients that NT-proBNP has a high sensitivity and specificity compared with ECHO to correctly diagnose patients with cardiac toxicity during adjuvant/neoadjuvant HER2 treatment.

Study Type

Interventional

Enrollment (Estimated)

700

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

  • Sweden
      • Gothenburg, Sweden, 432 45
        • Recruiting
        • Jubileumskliniken, Sahlgrenska 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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histological confirmed HER2 positive primary BC planned for adjuvant/neoadjuvant treatment with chemotherapy plus HER2 blocking agents.
  2. Patients ≥18 years
  3. ECOG/WHO 0-1
  4. Adequate organ function for the planned treatment according to local guidelines.
  5. No distant metastasis (CT/MRI only if clinically indicated).
  6. Negative pregnancy test within 14 days prior to start of treatment.
  7. If of childbearing potential, willing to use an effective form of contraception.
  8. No other malignancy during the last 5 years except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix.
  9. Signed informed consent and willingness to follow the trial procedures.

Exclusion Criteria:

  1. Patients with previous heart disease recommended special follow-up during treatment with high risk of termination of treatment.
  2. Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, neurological conditions, physical examination or laboratory findings) that may interfere with the planned treatment or affect patient compliance.
  3. Pregnancy and breast feeding.

  4. Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in situ).

    -

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: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NT-proBNP instead of ECHO/MUGA at 6 months and 12 months
Replacement with measurement of plasma levels of NT-proBNP at 6 months and 12 months instead of ECHO/MUGA for monitoring of trastuzumab-induced cardiotoxicity
Diagnostic test: Plasma NT-proBNP
Replacement of measurement of plasma NT-proBNP instead of ECHO/MUGA at 6 months and 12 months of trastuzumab treatment to assess cardiotoxicity

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity and specificity of NT-proBNP to detect trastuzumab-induced cardiotoxicity
Time Frame: From inclusion to 24 months after baseline investigation
To determine the sensitivity and specificity of NT-proBNP for identification of patients that develop cardiac toxicity during treatment with HER2 blocking agents for primary breast cancer [time frame from inclusion to 24 months after base-line investigation]
From inclusion to 24 months after baseline investigation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of trastuzumab-induced cardiotoxicity
Time Frame: From inclusion to 24 months after baseline investigation
To determine the proportion of patients that develop cardiac toxicity during treatment with HER2 blocking agents for primary breast cancer
From inclusion to 24 months after baseline investigation
Anthracycline-induced change in NT-proBNP
Time Frame: From inclusion to 10 weeks after baseline investigation

To investigate the potential change of NT-proBNP during anthracycline-based chemotherapy in patients that receive EC followed by anti-HER2 blockade plus a taxane and whether it is correlated with the development of cardiac toxicity throughout anti-HER2 blockade.

[time frame from inclusion to 10 weeks after base-line investigation]
From inclusion to 10 weeks after baseline investigation

Collaborators and Investigators

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

Sponsor

Vastra Gotaland Region

Investigators

  • Principal Investigator: Daniel Giglio, Assoc Prof, Sahlgrenska University Hospital/University of Gothenburg
  • Principal Investigator: Barbro Linderholm, Assoc Prof, Sahlgrenska University Hospital/University of Gothenburg

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)

March 14, 2024

Primary Completion (Estimated)

March 14, 2029

Study Completion (Estimated)

March 14, 2029

Study Registration Dates

First Submitted

March 25, 2024

First Submitted That Met QC Criteria

March 29, 2024

First Posted (Actual)

April 1, 2024

Study Record Updates

Last Update Posted (Actual)

April 1, 2024

Last Update Submitted That Met QC Criteria

March 29, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HER2BNP

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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