Clinical trial NCT01554943: Late Cardiac Evaluation of the Three Arm Belgian Trial Involving Node-positive Early Breast Cancer Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: CMF
HEC
EC
node positive
breast cancer
Lead sponsor: Jules Bordet Institute
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Universitaire de Tivoli
name: Clinique Sainte Elisabeth
name: Centre Hospitalier Jolimont-Lobbes
name: Réseau Hospitalier Médecine Sociale d'Ath
name: Hôpital de Braine-l'Alleud
First posted: 2012-03-15
Enrollment: 73
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Late cardiac toxicity
timeFrame: Exams will be performed only once, which will take place several years after the completion of chemotherapy (up to 15 years)
Secondary outcomes:
measure: Late cardiac and cognitive toxicity
timeFrame: Exams will be performed only once, which will take place several years after the completion of chemotherapy (up to 15 years)
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Jules Bordet Institute
Study officials:
affiliation: Jules Bordet Institute
name: Evandro de Azambuja, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, Tagnon A, Ries F, Gobert P, Finet C, Closon-Dejardin MT, Dufrane JP, Kerger J, Liebens F, Beauvois S, Bartholomeus S, Dolci S, Lobelle JP, Paesmans M, Nogaret JM. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001 Jun 15;19(12):3103-10. doi: 10.1200/JCO.2001.19.12.3103.
citation: de Azambuja E, Paesmans M, Beauduin M, Vindevoghel A, Cornez N, Finet C, Ries F, Closon-Dejardin MT, Kerger J, Gobert P, Focan C, Tagnon A, Dolci S, Nogaret JM, di Leo A, Piccart-Gebhart MJ. Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study. J Clin Oncol. 2009 Feb 10;27(5):720-5. doi: 10.1200/JCO.2008.17.2155. Epub 2008 Dec 22.
citation: de Azambuja E, Ameye L, Diaz M, Vandenbossche S, Aftimos P, Bejarano Hernandez S, Shih-Li C, Delhaye F, Focan C, Cornez N, Vindevoghel A, Beauduin M, Lemort M, Paesmans M, Suter T, Piccart-Gebhart M. Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy. Eur J Cancer. 2015 Nov;51(17):2517-24. doi: 10.1016/j.ejca.2015.08.011. Epub 2015 Aug 27.