CardioPROTECTion With Dapagliflozin in Breast Cancer Patients Treated With AnthrAcycline - PROTECTAA TRIAL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

4 Wojskowy Szpital Kliniczny Z Polikliniką Samodzielny Publiczny Zaklad Opieki Zdrowotnej We Wroclawiu

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

15 Apr 2024 → ongoing

Decision date (initial)

2023-11-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medical Research Agency, 1A Stanisława Moniuszki Street, 00-014 Warszawa

External identifiers

EU CT number

2023-506631-15-00

ClinicalTrials.gov

NCT06304857

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others, Therapy

Assessment of the effect of administered dapagliflozin compared to placebo on the occurrence of cancer therapeutics-related cardiac dysfunction (CTRCD) at 12 months.

Secondary objectives 4

1. Assessment of the effect of dapagliflozin compared with placebo on the occurrence of CTRCD in breast cancer patients after a 6-months- treatment period.
2. Assessment of the effect of dapagliflozin versus placebo on left ventricular diastolic function, change in Troponin I, NtproBNP and quality of life at 6 and 12 months.
3. Assessment of dapagliflozin tolerability and safety - comparing dapagliflozin and placebo groups by incidence: death from any cause, composite endpoint of cardiovascular events (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke), hypoglycaemia, ionic disorders, renal failure, drug hypersensitivity, allergic reactions, infections and any other AEs, evaluated due to type, frequency and severity.
4. Evaluation of the effect of administered dapagliflozin versus placebo on quality of life using the five dimensional EQ 5D questionnaire.

Conditions and MedDRA coding

Patients with invasive breast cancer, on stage I-III, and planned anthracycline treatment within 60 days.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Age > 18 years and < 80 years.
2. Diagnosis of invasive breast cancer [ stage I-III ] and planned anthracycline treatment within 60 days.
3. Signed Informed Consent to participate in the study.

Exclusion criteria 23

1. Urinary tract infection with the need for treatment with an antibiotic 48 hours before the scheduled start of anthracycline treatment.
2. BMI > 40 kg/m2.
3. Diagnosed type 1 or type 2 diabetes or fasting glucose ≥ 126 mg/dl or HbA1C ≥ 6,5% (48 mmol/mol) including newly diagnosed at screening.
4. Pregnancy or breastfeeding.
5. Lack of compliance to use highly effective method of birth control.
6. Expected or possible treatment with epirubicin or liposomal doxorubicin within 12 months.
7. Taking another study drug or drugs from the group of SGLT2 inhibitors up to 6 months before the screening visit.
8. Taking semaglutide, liraglutide and metformin during the 30 days preceding the screening visit.
9. eGFR < 25 ml/min/1.73m2 according to CKD EPI.
10. Life expectancy < 12 months or cancer disease stage IV according to the TNM classification.
11. ALAT/ ASPAT above 2.5 times the local norm.
12. Recognised heart failure or symptoms which, in the opinion of the investigator may be a symptom of undiagnosed heart failure.
13. Anemia with Hgb < 9 g/dl.
14. Liver disorders, Child-Pugh classification > 4points
15. Known, active infections with HIV, HBV, HCV, tuberculosis.
16. Any other condition which, in the opinion of the investigator, makes it impossible to fulfil the requirements for participation in this study.
17. Left ventricular ejection fraction < 50% at the time of the screening.
18. Severe valvular heart disease.
19. A history of clinically significant arrhythmia, including atrial fibrillation regardless of type (at discretion of the investigator).
20. A history of stroke.
21. Cardiomyopathy: congenital, post-inflammatory, toxic, infiltrative (e.g. amyloidosis, sarcoidosis, haemochromatosis), postnatal or hypertrophic.
22. Pulmonary hypertension.
23. Uncontrolled high arterial pressure or systolic pressure < 80 mmHg at screening at the discretion of the investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Primary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction, CTRCD):
2. the appearance of heart failure symptoms (NYHA class I-IV) due to an impairment of heart function or structure within 12 months; or
3. asymptomatic decrease in left ventricular ejection fraction > 10% after 12 months; or
4. asymptomatic decrease in left ventricular ejection fraction < 10% but up to 40-49% after 12 months; or
5. asymptomatic decrease in global left ventricular longitudinal strain >15% after 12 months; or
6. asymptomatic increase in biomarkers (troponin I > upper reference limit (99th centile) and increase of at least 30% from pre-treatment concentration or NTproBNP > 125 pg/ml and increase of at least 30% from baseline) after 12 months.

Secondary endpoints 25

1. Secondary Composite Efficacy Endpoint:
2. 1. emergence of heart failure symptoms (NYHA class I-IV) due to impaired cardiac function or structure at 6 months; or
3. 2. decrease LVEF > 10% after 6 months; or
4. 3. decrease LVEF < 10% but to a value of 40-49% after 6 months; or
5. 4. a decrease in global longitudinal strain of > 15% after 6 months; or
6. 5. asymptomatic increase in biomarkers (troponin I > upper reference limit (99th centile) and an increase of at least 30% from pre-treatment concentration or NTproBNP > 125pg/ml and an increase of at least 30% from baseline) after 6 months.
7. Secondary Additional Endpoints:
8. 1. change in left ventricular ejection fraction at 6 and 12 months;
9. 2. change in left ventricular diastolic function, assessed as the ratio of E/E', i.e. maximum mitral annular inflow velocity during the rapid ventricular filling phase, to maximum mitral annular motion velocity by tissue Doppler during the rapid ventricular filling phase;
10. 3. change in Troponin I after 6 and 12 months;
11. 4. change in NTproBNP levels at 6 and 12 months;
12. 5. change in quality of life assessment at 6 and 12 months.
13. Secondary Endpoints (Safety):
14. 1. death from any cause;
15. 2. composite endpoint of cardiovascular events (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke);
16. 3. death from any cardiovascular reasons;
17. 4. non-fatal myocardial infarction;
18. 5. non-fatal stroke;
19. 6. occurrence of hypoglycaemia;
20. 7. occurrence of ionic disorders;
21. 8. progression of renal failure;
22. 9. hypersensitivity to investigated drug;
23. 10. allergic reactions;
24. 11. infection.
25. 12. any other AEs, evaluated due to type, frequency and severity.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

4 Wojskowy Szpital Kliniczny Z Polikliniką Samodzielny Publiczny Zaklad Opieki Zdrowotnej We Wroclawiu

Sponsor organisation

4 Wojskowy Szpital Kliniczny Z Polikliniką Samodzielny Publiczny Zaklad Opieki Zdrowotnej We Wroclawiu

Address

Ul. Rudolfa Weigla 5

City

Wroclaw

Postcode

50-981

Country

Poland

Scientific contact point

Organisation

4 Wojskowy Szpital Kliniczny Z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej We Wroclawiu

Contact name

Lead Principal Investigator

Public contact point

Organisation

4 Wojskowy Szpital Kliniczny Z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej We Wroclawiu

Contact name

National Coordinator

Third parties 2

Locations

1 EU/EEA country · 3 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 11 files

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

Application history

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