Late Cardiac Evaluation of the Three Arm Belgian Trial Involving Node-positive Early Breast Cancer Patients

Study Overview
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Brief Summary
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Late Cardiac Evaluation of the Three Arm Belgian Trial A phase III randomized trial involving node-positive early breast cancer patients with a long median follow-up (  15 years) OBJECTIFS Primary: • To compare the incidence of late cardiac events between anthracycline and non-anthracycline chemotherapy given to node-positive breast cancer patients in the Belgian three arm randomized clinical trial Secondary: To compare the late incidence of cardiac events between higher and lower dose anthracycline treated node-positive breast cancer patients; To compare anthracyclines (higher and lower doses) and non-anthracycline chemotherapy for: left ventricular diastolic function assessed by Echo exercise capacity assessed by 6-minute walk test (6MWT) cardiac morphology (myocardial inflammation or injury, fibrosis, LVEF) assessed by MRI serum cardiac biomarkers (BNP and TNT) patient-reported cardiac symptoms patient-reported cardiac symptoms assessed by QOL questionnaires are associated with subclinical findings on LVEF assessment cognitive function, functional autonomy, and psychological distress

Detailed Description
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The primary objective of this study is to compare the incidence of cardiac events [(defined as asymptomatic systolic dysfunction (LVEF < 50%, asymptomatic NYHA I) or symptomatic heart failure NYHA class II-IV either by Echo and/or by clinical exam (LVEF < 50% and heart failure symptoms)] between anthracycline and non-anthracycline chemotherapy treated node-positive breast cancer patients in a long-term follow-up. We will define a binary status for each patient: no cardiac event / one or more cardiac events. Analysis of the primary endpoint will involve a comparison of the CMF-treated patients versus the pooled anthracycline treated patients (EC and HEC). If a significant difference is detected, all paired comparisons will also be performed for the primary endpoint (CMF versus EC, CMF versus HEC, EC versus HEC).

Official Title
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Late Cardiac Evaluation of the Three Arm Belgian Trial A Phase III Randomized Trial Involving Node-positive Early Breast Cancer Patients With a Long Median Follow-up (  15 Years)

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: cardiac MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Alive, free of any recurrence, Not lost to follow-up Last workup should be no older than 1 year to exclude relapses. If this is older than 1 year, a new workup (PE, blood tests and MMG) will be performed prior to the entry in this study Patients previously diagnosed with CHF who are free of recurrence will also be invited to participate, if there is no contra-indication Patients should be able to perform the prescribed assessments Exclusion Criteria: Death Breast cancer recurrence Unwilling to perform exams as per protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CMF<br>adjuvant standard CMF given from 1988 to 1996 | Other: cardiac MRI<br>* Patients will be submitted to extensive cardiac evaluation several years after completion of adjuvant chemotherapy<br>|
| Experimental: EC<br>Adjuvant EC chemotherapy given from 1988 to 1996 | Other: cardiac MRI<br>* Patients will be submitted to extensive cardiac evaluation several years after completion of adjuvant chemotherapy<br>|
| Experimental: HEC<br>High dose epirubicin (HEC) given from 1988 to 1996 | Other: cardiac MRI<br>* Patients will be submitted to extensive cardiac evaluation several years after completion of adjuvant chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late cardiac toxicity | The primary objective of this study is to compare the incidence of cardiac events [(defined as asymptomatic systolic dysfunction (LVEF < 50%, asymptomatic NYHA I) or symptomatic heart failure NYHA class II-IV either by Echo and/or by clinical exam (LVEF < 50% and heart failure symptoms)] between anthracycline and non-anthracycline chemotherapy. Analysis of the primary endpoint will involve a comparison of the CMF-treated patients versus the pooled anthracycline treated patients (EC and HEC). | Exams will be performed only once, which will take place several years after the completion of chemotherapy (up to 15 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late cardiac and cognitive toxicity | To compare the late incidence of cardiac events between higher and lower dose anthracycline treated node-positive breast cancer patients; To compare anthracyclines (higher and lower doses) and non-anthracycline chemotherapy for: LVEF assessed by Echo; exercise capacity assessed by 6-minute walk test; cardiac morphology assessed by MRI; serum cardiac biomarkers; patient-reported cardiac symptoms assessed by QOL questionnaires; cognitive function, functional autonomy, and psychological distress | Exams will be performed only once, which will take place several years after the completion of chemotherapy (up to 15 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CMF, HEC, EC, node positive, breast cancer