Clinical trial NCT04790266: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cardiotoxicity
Lead sponsor: Oncology Institute of Southern Switzerland
Sponsor class: OTHER
Collaborators: name: Cardiocentro Ticino
name: North Estonia Medical Centre
name: Fondazione IRCCS Policlinico San Matteo di Pavia
First posted: 2021-03-10
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: CMR T2 mapping
timeFrame: Time window of 12 months from the end of radiation therapy
Secondary outcomes:
measure: GLS
timeFrame: Time window of 12 months from the end of radiation therapy
measure: Myocardial edema
timeFrame: Time window of 12 months from the end of radiation therapy
measure: Biomarkers (Troponine, pro-BNP, hs-CRP) correlate with LVEF
timeFrame: Time window of 12 months from the end of radiation therapy
measure: Biomarkers (Troponine, pro-BNP, hs-CRP) correlated with GLS
timeFrame: Time window of 12 months from the end of radiation therapy
measure: Time to biomarkers (Troponine, pro-BNP, hs-CRP) increase
timeFrame: Time window of 12 months from the end of radiation therapy
measure: Biomarkers (Troponine, pro-BNP, hs-CRP) predictors of cardiotoxicity
timeFrame: Time window of 12 months from the end of radiation therapy
measure: Major cardiovascular events
timeFrame: follow-up
measure: cardiac fibrosis
timeFrame: through study completion, an average of 1 year
measure: acute asymptomatic pericarditis
timeFrame: through study completion, an average of 1 year
measure: cardiac edema
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Italian Switzerland
state: Ticino
Study officials:
affiliation: IOSI
name: mariacarla Valli
role: PRINCIPAL_INVESTIGATOR
References:
citation: Borgonovo G, Vettus E, Greco A, Leo LA, Faletra FF, Klersy C, Curti M, Valli M. Early Detection of Cardiotoxicity From Systemic and Radiation Therapy in Patients With Breast Cancer: Protocol for a Multi-Institutional Prospective Study. JMIR Res Protoc. 2022 Apr 21;11(4):e31887. doi: 10.2196/31887.