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Early Detection of Cardiotoxicity From Systemic and Radiation Therapy in Breast Cancer Patients (CARDIOTOX)

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ClinicalTrials.gov Identifier: NCT04790266
Recruitment Status : Recruiting
First Posted : March 10, 2021
Last Update Posted : March 10, 2021
Sponsor:
Collaborators:
Cardiocentro Ticino
North Estonia Medical Centre
Fondazione IRCCS Policlinico San Matteo di Pavia
Information provided by (Responsible Party):
Oncology Institute of Southern Switzerland

Tracking Information
First Submitted Date February 23, 2021
First Posted Date March 10, 2021
Last Update Posted Date March 10, 2021
Actual Study Start Date September 15, 2020
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 5, 2021)
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%).
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: March 5, 2021)
  • 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
  • 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.
  • 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.
  • 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 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.
  • 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%.
  • 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
  • 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
  • acute asymptomatic pericarditis [ Time Frame: through study completion, an average of 1 year ]
    incidence of acute asymptomatic pericarditis after radiation therapy, measured on CMR
  • 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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Early Detection of Cardiotoxicity From Systemic and Radiation Therapy in Breast Cancer Patients
Official Title Early Detection of Cardiotoxicity From Systemic and Radiation Therapy in Breast Cancer Patients
Brief Summary 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%) measured on CMR and ECHO over the time window of 12 months from the end of radiation therapy.
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 Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
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

Condition Cardiotoxicity
Intervention Diagnostic Test: Cardiac MRI
cCardiac MRI, ecocardiography and cardiotoxicity blood tests will be repeated as previously scheduled
Other Names:
  • Echocardiography
  • Cardiotoxicity laboratory tests (troponin, Pro-BNP, hsCRP)
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: March 5, 2021)
150
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  1. Written informed consent must be obtained before any assessment is performed
  2. Age ≥ 18 years at visit 1
  3. Performance status ECOG 0-1
  4. *Stage I-III histology proven breast cancer
  5. Treated with adjuvant radiotherapy and neo/adjuvant anthracycline and/or trastuzumab-based therapy +/- hormonal therapy
  6. 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:

  1. Known metastatic spread of any cancer
  2. Known active or recurrent hepatic disorder (cirrhosis, hepatitis), ASAT/ALAT 2xULN
  3. Renal function decrease (eGFR < 30 ml/min)
  4. Known coronary artery disease
  5. Angina pectoris
  6. Positive or missing pregnancy test (pre- and perimenopausal women) at enrolment visit
  7. Patients with baseline LVEF <53% and GLS <15%
  8. Patients with pacemaker
Sex/Gender
Sexes Eligible for Study: Female
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Valli 0041918119430 mariacarla.valli@eoc.ch
Contact: Borgonovo 0041918118926 giulia.borgonovo2@eoc.ch
Listed Location Countries Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number NCT04790266
Other Study ID Numbers 2019-01395CE3508
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Oncology Institute of Southern Switzerland
Study Sponsor Oncology Institute of Southern Switzerland
Collaborators
  • Cardiocentro Ticino
  • North Estonia Medical Centre
  • Fondazione IRCCS Policlinico San Matteo di Pavia
Investigators
Principal Investigator: mariacarla Valli IOSI
PRS Account Oncology Institute of Southern Switzerland
Verification Date February 2021