Clinical trial NCT04541212: Identification and Evaluation of Patients at Risk of Developing Cardiotoxicity After Receiving Chemotherapy for Breast Cancer, Lymphoma or Leukemia
Official title: Identification and Evaluation of Patients at Risk of Developing Cardiotoxicity After Receiving Chemotherapy for Breast Cancer, Lymphoma or Leukemia
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Breast Cancer
Lymphoma
Leukemia
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2020-09-09
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 225 patients enrolled from oncology clinics. Patients will be screened and identified at the oncology clinics. The prospective cardiac evaluations including New York Heart Association (NYHA) functional classification, transthoracic echocardiography, CMR, standard 12-lead electrocardiogram (ECG), cardiac biomarkers, lipid profile \& HDL functionality tests will be performed at the Montreal Heart Institute (MHI).

Brief summary: This is an observational study of the occurrence of cardiac toxicity in patients with breast cancer,lymphoma or leukemia receiving chemotherapy including an anthracycline. Patients will be identified at the oncology clinic and will be included in the study if all eligible criteria are met. The study will involve retrospective and prospective evaluations.

Safety will be assessed through reporting of serious adverse events (SAEs) related to study procedures.

Detailed description: The aim of this study is to identify and evaluate cardiotoxicity in patients with diagnosis of breast cancer, lymphoma or leukemia scheduled to receive anthracycline-based chemotherapy (Cohort A: prospective evaluation); and patients undergoing or having received within the last 5 years anthracycline-based chemotherapy (Cohort B: retrospective and prospective evaluations). Part A and B will be conducted in parallel. This study also has the objectif of identifying biomarkers of cardiotoxicity including inflammatory response proteins and clonal hematopoiesis.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older at time of CT initiation
* Signed informed consent
* Patients with diagnosis of breast cancer,lymphoma or leukemia (including autografted subjects)
* Planned, ongoing or completed (within last 5 years) chemotherapy with anthracycline
* Left ventricular ejection fraction (LVEF) ≥50% pre-chemotherapy
* The participant is willing to undergo CMR scans and all other required study procedures

Exclusion Criteria:

* Known cardiomyopathy and/or LVEF \<50%
* Known heart failure
* History of myocardial infarction (MI)
* Clinically significant cardiac valvular disease
* Clinically significant pericardial effusion
* Allografted subjects
* Contraindications to CMR testing (Cohort A \& prospective evaluation for Cohort B):

  * Pacemakers, other metallic implants or severe claustrophobia
  * Weight \> 135 kg
  * Patients with a history of previous allergic reaction to gadolinium
  * Patients with history of seizure
  * Renal insufficiency (eGFR of \< 45ml/min/1.73m2 using the MDRD equation)
  * Pregnant or breastfeeding women

Primary outcomes:
measure: Myocardial extracellular volume (ECV)
timeFrame: Change from baseline to 3, 6, 12,and 24 months
measure: Myocardial extracellular volume (ECV)
timeFrame: Change from baseline to prior study entry, 12 and 24 months post study entry.
Secondary outcomes:
measure: Left ventricular (LV) systolic function (global and regional)
timeFrame: Change from baseline to 3, 6, 12,and 24 months.
measure: Biomarker of myocardial injury (high-sensitivity troponin (hs-cTn))
timeFrame: Change from baseline to 3, 6, 12,and 24 months.
measure: Biomarker of elevated LV fitting pressure (N-Terminal-pro-hormone B-type Natriuretic Peptide (NT-proBNP))
timeFrame: Change from baseline to 3, 6, 12,and 24 months.
measure: Biomarker of inflammation (high-sensitivity C-reactive protein (hs-CRP))
timeFrame: Change from baseline to 3, 6, 12,and 24 months.
measure: Clonal hematopoiesis associated gene mutations.
timeFrame: Change from baseline to 24 months..
measure: Telomere length measurement
timeFrame: Change from baseline to 24 months..
measure: Left ventricular (LV) systolic function (global and regional)
timeFrame: Change from study entry to 12 and 24 months.
measure: Biomarker of myocardial injury (high-sensitivity troponin (hs-cTn))
timeFrame: Change from study entry to 12 and 24 months.
measure: Biomarker of elevated LV fitting pressure (N-Terminal-pro-hormone B-type Natriuretic Peptide (NT-proBNP))
timeFrame: Change from study entry to 12 and 24 months.
measure: Biomarker of inflammation (high-sensitivity C-reactive protein (hs-CRP))
timeFrame: Change from study entry to 12 and 24 months.
measure: Clonal hematopoiesis associated gene mutations.
timeFrame: Change from baseline to 24 months..
measure: Telomere length measurement
timeFrame: Change from baseline to 24 months..
Other outcomes:
Locations:
city: Terrebonne
country: Canada
facility: CISSSS de Lanaudière_Hôpital Pierre LeGardeur (referring site)
state: Quebec (QC)
city: Montreal
country: Canada
facility: Centre Hospitalier de l'université de Montréal (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: CIUSSS Ouest de l'ile de Montreal - St-Mary's Hospital
state: Quebec
city: Montréal
country: Canada
facility: CIUSSS de l'Est-de-l'Île-de-Montréal - Hôpital Maisonneuve-Rosemont
state: Quebec
city: Montréal
country: Canada
facility: CIUSSS du Centre-Ouest de l'Île de Montréal - Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Jean-Claude Tardif, MD
role: PRINCIPAL_INVESTIGATOR
References: