Sacubitril/Valsartan in prevention of heart damage during breast cancer treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Slaskie Centrum Chorob Serca W Zabrzu

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

17 Apr 2024 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medical Research Agency

External identifiers

EU CT number

2024-517804-12-00

EudraCT number

2022-003046-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Prophylaxis, Therapy

Estimation of whether prophylactic use of sacubitril/valsartan will prevent cardiotoxicity associated with systemic breast cancer treatment, defined as a decrease in left ventricular ejection fraction ≥ 5% in an ultrasound scan during 24 months from randomization.

Secondary objectives 5

1. Estimation of whether NT-proBNP and troponin markers can be used as indicators of the prevention of cardiotoxicity associated with systemic treatment of sacubitril/valsartan breast cancer.
2. Estimation of genetic correlation with prevention of cardiotoxicity associated with systemic treatment of breast cancer with sacubitril/valsartan.
3. Estimation of the reversibility of cardiotoxicity associated with systemic breast cancer treatment defined as a decrease in left ventricular ejection fraction.
4. Comparison of the detection sensitivity of cardiotoxicity associated with systemic treatment of breast cancer defined as a decrease in LVEF ≥ 5% in ultrasound examination with other imaging tests – ultrasound of the heart (UKG-echocardiography)
5. Estimation of the role of novel markers of cardiotoxicity (myeloperoxidase (MPO), galectin 3, GDF-15 protein and circulating receptor for IL-33 (sST2), but other considered biomarkers (PIGF, suPAR) and potential genomic markers (microRNAs)

Conditions and MedDRA coding

Heart failure – post-anthracycline cardiomyopathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Written informed consent
2. Female gender, aged 18 years and over
3. Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (ER, PR, HER2, Ki67)
4. Ability to take oral medication and willingness to adhere to the planned regimen
5. Tumor grade IA-IIIC or oligometastatic grade IV
6. Radical treatment plan including surgery or post-radical surgical treatment
7. Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and/or anti-HER2 drugs
8. ECOG 0-2 general status
9. LVEF ≥ 50% as assessed by echocardiography
10. Sinus rhythm

Exclusion criteria 13

1. Lack of Written informed consent
2. Prior anthracycline-based chemotherapy and/or left-sided radiotherapy (prior to diagnosis of the cancer being the present cause of XML File Identifier: xW+Ea9mm17kcx3fLB1UWMlFS0h4=Page 16/27 therapy)
3. Clinically relevant HF (NYHA II-IV)
4. MI within the last < 3 months
5. Symptomatic hypotension or SBP < 90 mmHg
6. Significant valvular disease, symptomatic coronary artery disease (CCS>2), significant AV block, symptomatic sinus node dysfunction
7. Expected survival <12 months
8. GFR<30 ml/min/1.73 m2 (screening visit)
9. K+>5.5mmol/L (screening visit)
10. Contraindications to ACE-I/ARB or LCZ696 if not listed among criteria
11. Active untreated liver disease
12. Pregnancy
13. Conditions/circumstances that may lead to non-compliance with medical staff recommendations (e.g. active drug/alcohol dependence, poorly controlled mental illness)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Decrease in left ventricular ejection fraction ≥ 5% assessed on magnetic resonance imaging (MRI) in 24 months from randomisation

Secondary endpoints 17

1. Death from any cause or hospitalization for heart failure
2. Death from any cause
3. Death from cardiovascular causes
4. Hospitalization for other cardiovascular causes
5. cardiotoxicity
6. Decrease in left ventricular ejection fraction ≥ 5% (MRI) during 24 months from randomization
7. Decrease in left ventricular ejection fraction ≥ 5% during 24 months from randomization
8. Occurrence of diastolic dysfunction (UKG) within 24 months of randomization Diastolic dysfunction assessed on echocardiography
9. Development of pathological pericardial fluid volume or increase in pericardial fluid volume from baseline
10. Occurrence of cardiac tamponade
11. Occurrence of pericarditis
12. Occurrence of myocarditis
13. Development of ventricular arrhythmias
14. Development of supraventricular arrhythmias
15. Presence of conduction disturbances
16. Changes in corrected QT interval
17. Changes in BNP, NT pro-BNP, troponin T or troponin I levels

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Slaskie Centrum Chorob Serca W Zabrzu

Sponsor organisation

Slaskie Centrum Chorob Serca W Zabrzu

Address

Ul. Marii Curie-Sklodowskiej 9

City

Zabrze

Postcode

41-800

Country

Poland

Scientific contact point

Organisation

Slaskie Centrum Chorob Serca W Zabrzu

Contact name

Clinical coordinator

Public contact point

Organisation

Slaskie Centrum Chorob Serca W Zabrzu

Contact name

Clinical coordinator

Third parties 1

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications