A Phase 3, Randomized, Double-blind, Placebo-controlled Study to evaluate Efficacy and Safety of Empagliflozin in the prevention of Cardiotoxicity in Cancer patients undergoing Chemotherapy based on Anthracyclines (EMPACT study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

6 Jul 2023 → ongoing

Decision date (initial)

2024-07-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Agencja Badań Medycznych (project ABM no.2021/ABM/03/00012)

External identifiers

EU CT number

2024-515495-13-00

EudraCT number

2022-003043-10

ClinicalTrials.gov

NCT05271162

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to evaluate the efficacy of empagliflozin 10 mg versus placebo in prevention of left ventricular (LV) dysfunction in cancer patients receiving high cumulative doses of anthracyclines

Secondary objectives 2

1. To compare the overall response rate (ORR) of subjects randomized to treatment with empagliflozin compared to placebo
2. To assess the safety and tolerability of empagliflozin compared to placebo

Conditions and MedDRA coding

Cardiotoxicity. The study population will consist of patients diagnosed with cancer, without history of heart failure and LV ejection fraction (EF) ≥ 50%, scheduled for high dose anthracyclines (doxorubicin ≥240 mg/m2 or epirubicin ≥360 mg/m2) as standard of care (SoC) systemic anticancer treatment.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Eastern Cooperative Oncology Group (ECOG) performance status from 0 to 2.
2. ≥ 18 years of age at the time of signing the informed consent.
3. Known neoplastic disease prior to the initiation of chemotherapy with a high dose of anthracyclines (doxorubicin ≥ 240 mg / m2 b.w. or epirubicin ≥ 360 mg / m2 b.w.)
4. No history of heart failure (left ventricular ejection fraction ≥ 50% as assessed by echocardiography).
5. Ability to give written informed consent and comply with protocol requirements.
6. Women of child-bearing age must have a negative serum or urine pregnancy test.
7. All males and females must consent to the use of effective contraception throughout the study period and after study medication is discontinued.
8. Women of childbearing potential (WOCBP) must meet and/or agree to all the following for contraception: a. use 2 effective methods of contraception (abstinence, IUD, oral contraceptive, or double barrier device) from informed consent and for at least 6 months after study drug discontinuation. b. agrees not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time period.
9. Sexually active men and their sexual partners must use effective methods of contraception from the moment they sign their informed consent to participate in the study and for at least 3 months after discontinuation of the study drug.

Exclusion criteria 15

1. History of heart failure.
2. Left ventricle systolic dysfunction assessed by echocardiography (LVEF<50%).
3. Significant valve disease
4. Previous chemotherapy or radiation to the chest.
5. Symptomatic hypotension and / or SBP <100 mmHg at Visit 1 or Visit 2.
6. Liver disease, as determined by Aspartate aminotransferase (AST) or alanine aminotransferase (ALT), or alkaline phosphatase levels above 3 x upper limit of normal (ULN) at Visit 1.
7. Renal impairment, defined as eGFR <20 mL / min / 1.73 m2 or dialysis requirement, as determined at Visit 1.
8. History of ketoacidosis.
9. Gastrointestinal surgery or gastrointestinal disturbance that could impair drug absorption.
10. Presence of any disease with a life expectancy <1 year in the opinion of the Investigator.
11. Treatment with any SGLT-2 inhibitor for up to 3 months prior to study enrolment.
12. Pregnant or lactating females.
13. Drug or alcohol abuse.
14. Suspected non-compliance and irregular use of study drug.
15. Inability to perform cardiac MRI due to, e.g., claustrophobia, weight> 120 kg.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first event of left ventricular systolic dysfunction. Criterion for the diagnosis of left ventricular systolic dysfunction in echocardiography: reduction of left ventricular ejection fraction (LVEF)> 10 percentage points from baseline to <50%

Secondary endpoints 2

1. Overall response rate 1. Composite secondary endpoint • all-cause death • cardiovascular death • myocardial infarction • stroke 2. Other: • decrease in GLS (global longitudinal strain) • structural myocardial alterations in CMR • changes in the concentration of biomarkers in blood samples (Troponin T, NTproBNP)
2. Incidence and intensity of Adverse events (AEs), including serious AEs (SAEs).Withdrawal from study drug due to AEs • Clinically relevant changes in laboratory assessments from baseline. • Clinically relevant new finding or worsening of existing condition on physical examination • Assessment of vital status. AESIs: ketoacidosis, lower limb amputation • Laboratory parameters: hematology, serum chemistry, lipids profile, and urinalysis.Physical Examination •Vital Status: SBP, DBP and pulse rate

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Sponsor organisation

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Address

Ul. Wilhelma Konrada Roentgena 5

City

Warsaw

Postcode

02-781

Country

Poland

Scientific contact point

Organisation

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Contact name

główny badacz

Public contact point

Organisation

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Contact name

główny badacz

Locations

1 EU/EEA country · 2 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 6 files

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

Application history

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