- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04790266
Early Detection of Cardiotoxicity From Systemic and Radiation Therapy in Breast Cancer Patients (CARDIOTOX)
Study Overview
Detailed Description
Overall study schedule The Overall Study Schedule is summarized in the assessment schedule (appendix 1).
This study is composed of three subsequent phases: a Run-In Phase, a RT/Systemic Therapy Phase, a Follow-Up Phase.
Run-In Phase The Run-In Phase starts with the first visit (before any cancer treatment), when Screening/Enrollment procedure is performed. This phase will start once a patient has provided WIC to participate in the study and ends the day of treatment start.
Screening / Enrolment Visit Visit will be performed before the expected starting date of treatment.
After a WIC has been obtained from the patient, the patient will be visited by the Investigators and the following information will be gathered:
- Demographic Data (age, height, weight, BMI);
- Medical history (previous and concomitant diseases, previous therapies, family history of CVD);
- Concomitant Medication;
- Physical examination & overall health assessment (including vital signs).
- Pregnancy test (pre- and perimenopausal women). The inclusion and exclusion criteria will be checked and, if the patient complies with all the Inclusion and Exclusion criteria, she will be enrolled into the study
A baseline assessment will be performed by the Investigator:
CMR, ECG and ECHO will be done at the participating centers The patient will be assigned to specific treatment (chemo/immunotherapy and adjuvant radiation therapy +/- aromatase inhibitor/tamoxifen/LhRh agonist). A standard of care treatment will be administered.
Radiotherapy/Systemic therapy Treatment Phase (specific Visit descriptions) SYSTEMIC TREATMENT Blood sample will be scheduled before and, if possible, 24 hours after chemotherapy administration.
- Patients treated with antracyclines regimens will be checked with ECG and ECHO at the end of treatment.
- Blood sample will be scheduled before Trastuzumab administration every three weeks and ECHO will be done after every 4 cycles (3 months).
RADIOTHERAPY For Technical details see appendix 3. Before starting RT patients will be checked clinically the first day of treatment and baseline tests will be done.
Biomarkers will be checked the first day and in the middle of RT. If a patient gets symptomatic heart failure during the treatment, or if LVEF decline greater than 10% points with a final LVEF <53% measured on Echo, the patient will be referred to the cardiologist for a specific treatment as described by guidelines
End of RT Group Patients treated with trastuzumab, will continue the treatment up to 1 year. Blood tests will be taken every three weeks and Echos will be done after every 4 cycles (3-week cycles).
Follow-Up Phase 2 weeks+/-3 days after the end of RT, blood sample will be taken. An ECHO and CMR will be done.
All patients will be checked 6 weeks after the end of radiotherapy for the study visit.
The following activities will be performed:
Blood sample for biomarkers. If hs-CRP ≥3mg/l, ECHO will be done. All patients will be followed at least until 10 years after the end of RT. Blood samples for measuring biomarkers and ECHO and CMR will be done 12 months after the end of RT.
Unscheduled Visit An unscheduled visit may occur at any time during the study, only for safety reason or for a premature discontinuation from the study.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
-
-
Ticino
-
Bellinzona, Ticino, Switzerland, 6500
- Recruiting
- Oncology Institute of Italian Switzerland
-
Contact:
- Giulia Borgonovo, MD
- Phone Number: 0041918118926
- Email: giulia.borgonovo@eoc.ch
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Female patients aged ≥ 18 years with stage I-III breast cancer treated with radiation therapy and neo/adjuvant chemo/immunotherapy +/- aromatase inhibitor/tamoxifen/LhRh agonist.
An ancillary study will enroll also stage 0 patients
Description
Inclusion Criteria:
- Written informed consent must be obtained before any assessment is performed
- Age ≥ 18 years at visit 1
- Performance status ECOG 0-1
- *Stage I-III histology proven breast cancer
- Treated with adjuvant radiotherapy and neo/adjuvant anthracycline and/or trastuzumab-based therapy +/- hormonal therapy
- Negative pregnancy test (plasma HCG) for all females of childbearing potential (i.e not permanently sterilised- post hysterectomy or tubal ligation status) In the ancillary study patients with stage 0 (DCIS) histology proven breast cancer will also be included.
Exclusion Criteria:
- Known metastatic spread of any cancer
- Known active or recurrent hepatic disorder (cirrhosis, hepatitis), ASAT/ALAT 2xULN
- Renal function decrease (eGFR < 30 ml/min)
- Known coronary artery disease
- Angina pectoris
- Positive or missing pregnancy test (pre- and perimenopausal women) at enrolment visit
- Patients with baseline LVEF <53% and GLS <15%
- Patients with pacemaker
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
CMR T2 mapping
Time Frame: Time window of 12 months from the end of radiation therapy
|
To assess the role of myocardial oedema on CMR (T2 mapping) after radiation therapy and cardiotoxic systemic therapy in predicting the incidence of cardiotoxicity, defined as by consensus guidelines* (decline of LVEF ≥10% points with a final LVEF <53%).
|
Time window of 12 months from the end of radiation therapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
GLS
Time Frame: Time window of 12 months from the end of radiation therapy
|
To detect GLS decrease >15% from baseline, measured on Echo over the time window of 12 months
|
Time window of 12 months from the end of radiation therapy
|
Myocardial edema
Time Frame: Time window of 12 months from the end of radiation therapy
|
To assess the incidence of myocardial oedema on CMR (T2 mapping) after radiation therapy and cardiotoxic systemic therapy. To assess the incidence of myocardial oedema on ECHO after radiation therapy and cardiotoxic systemic therapy. |
Time window of 12 months from the end of radiation therapy
|
Biomarkers (Troponine, pro-BNP, hs-CRP) correlate with LVEF
Time Frame: Time window of 12 months from the end of radiation therapy
|
To see if the changes in Troponine (ng/L) will correlate with LVEF measurements, assessed by ECHO. To see if the changes in Troponine (ng/L) will correlate with LVEF measurements, assessed by CMR. To see if the changes in pro-BNP (ng/L) will correlate with LVEF measurements, assessed by ECHO. To see if the changes in pro-BNP (ng/L) will correlate with LVEF measurements, assessed by CMR. To see if the changes in hs-CRP (mg/L) will correlate with LVEF measurements, assessed by ECHO. To see if the changes in hs-CRP (mg/L) will correlate with LVEF measurements, assessed by CMR. |
Time window of 12 months from the end of radiation therapy
|
Biomarkers (Troponine, pro-BNP, hs-CRP) correlated with GLS
Time Frame: Time window of 12 months from the end of radiation therapy
|
To see if the changes in Troponine (ng/L) will correlate with GLS measurements, assessed by ECHO. To see if the changes in pro-BNP (ng/L) will correlate with GLS measurements, assessed by ECHO. To see if the changes in hs-CRP (mg/L) will correlate with GLS measurements, assessed by ECHO. |
Time window of 12 months from the end of radiation therapy
|
Time to biomarkers (Troponine, pro-BNP, hs-CRP) increase
Time Frame: Time window of 12 months from the end of radiation therapy
|
To compare the time to the Troponine (ng/L) positivity to the time to the decrease in GLS >15% and/or decline of LVEF ≥10% points with a final LVEF <53% measured on Echo. To compare the time to the pro-BNP (ng/L) positivity to the time to the decrease in GLS >15% and/or decline of LVEF ≥10% points with a final LVEF <53% measured on Echo. To compare the time to the hs-CRP (mg/L) positivity to the time to the decrease in GLS >15% and/or decline of LVEF ≥10% points with a final LVEF <53% measured on Echo. |
Time window of 12 months from the end of radiation therapy
|
Biomarkers (Troponine, pro-BNP, hs-CRP) predictors of cardiotoxicity
Time Frame: Time window of 12 months from the end of radiation therapy
|
To see if the changes in Troponine (ng/L) will correlate with developement of cardiotoxicity, defined as by decline of LVEF ≥10% points with a final LVEF <53%. To see if the changes in pro-BNP (ng/L) will correlate with developement of cardiotoxicity, defined as by decline of LVEF ≥10% points with a final LVEF <53%. To see if the changes in hs-CRP (mg/L) will correlate with developement of cardiotoxicity, defined as by decline of LVEF ≥10% points with a final LVEF <53%. |
Time window of 12 months from the end of radiation therapy
|
Major cardiovascular events
Time Frame: follow-up
|
To detect major cardiovascular events (defined as acute myocardial infarction, hospitalization due to heart failure, atrial flutter/fibrillation, ventricular tachycardia) or death due cardiac problems during the follow up
|
follow-up
|
cardiac fibrosis
Time Frame: through study completion, an average of 1 year
|
assess the role of fibrosis on CMR (T1 mapping with evaluation of extracellular volume) after cardiotoxic radiation therapy and systemic therapy in predicting the incidence of cardiotoxicity
|
through study completion, an average of 1 year
|
acute asymptomatic pericarditis
Time Frame: through study completion, an average of 1 year
|
incidence of acute asymptomatic pericarditis after radiation therapy, measured on CMR
|
through study completion, an average of 1 year
|
cardiac edema
Time Frame: through study completion, an average of 1 year
|
investigate if the area of the edema on CRM correlates with RT dose distribution
|
through study completion, an average of 1 year
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2019-01395CE3508
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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