NT-proBNP to Assess Trastuzumab-induced Cardiotoxicity

NCT ID: NCT06340516

Last Updated: 2024-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-14

Study Completion Date

2029-03-14

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cardiotoxicity Breast Cancer Treatment Side Effects

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This is a national multicentre phase II trial investigating the sensitivity and specificity of NT-proBNP for the diagnose of cardiac toxicity during primary anti-HER2 blockade. NT-proBNP is compared with the todays´ standard (ECHO/MUGA).
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Plasma NT-proBNP

Intervention Type DIAGNOSTIC_TEST

Replacement of measurement of plasma NT-proBNP instead of ECHO/MUGA at 6 months and 12 months of trastuzumab treatment to assess cardiotoxicity

Interventions

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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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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).

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Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vastra Gotaland Region

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Giglio, Assoc Prof

Role: PRINCIPAL_INVESTIGATOR

Sahlgrenska University Hospital/University of Gothenburg

Barbro Linderholm, Assoc Prof

Role: PRINCIPAL_INVESTIGATOR

Sahlgrenska University Hospital/University of Gothenburg

Locations

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Jubileumskliniken, Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status RECRUITING

Countries

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Sweden

Central Contacts

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Daniel Giglio, Assoc Prof

Role: CONTACT

+46(0)31-342 16 06

Facility Contacts

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Daniel Giglio, Assoc Prof

Role: primary

+46(0)31-342 16 06

Other Identifiers

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HER2BNP

Identifier Type: -

Identifier Source: org_study_id

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