Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
316
Countries
1
Sites
9
Chemotherapy-induced cardiotoxicity in breast cancer
The study seeks primarily to assess whether the administration of dapagliflozin is associated with a lower rate of asymptomatic and symptomatic CTRCD during 18 months
Key facts
- Sponsor
- Fondazione IRCCS Policlinico San Matteo
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Cardiovascular Diseases [C14]
- Trial duration
- 3 Dec 2024 → ongoing
- Decision date (initial)
- 2024-12-03
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-518611-18-00
- EudraCT number
- 2022-003377-28
- ClinicalTrials.gov
- NCT06341842
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy
The study seeks primarily to assess whether the administration of dapagliflozin is associated with a lower rate of asymptomatic and symptomatic CTRCD during 18 months
Secondary objectives 6
- Demonstrate whether dapagliflozin reduces the excess risk associated with trastuzumab
- Demonstrate the reduction of rate of asymptomatic mild CTRCD in the dapagliflozin group during 18 months
- Demonstrate the reduction of rate of asymptomatic moderate CTRCD in the dapagliflozin group during 18 months.
- Demonstrate the reduction of rate of asymptomatic severe CTRCD in the dapagliflozin group during 18 months
- Demonstrate the reduction of rate of symptomatic CTRCD in the dapagliflozin group during 18 months
- Assess efficacy of dapagliflozin on improvement of diastolic function, end systolic and diastolic left ventricular volumes and plasma levels of bio-humoral markers, compared to standard of care during 18 months.
Conditions and MedDRA coding
Chemotherapy-induced cardiotoxicity in breast cancer
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Chemotherapy-naive patients, scheduled for antracycline +/- trastuzumab treatment in the (neo-)adjuvant setting for stage I-III breast cancer
- Adult women between 18 and 70 years of age
- eGFR>25 ml/min/1.7 mq
- ECOG score 0-2Consent form signed.
- Female patients of childbearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have a negative result from a serum pregnancy test performed within 7 days of randomization and on the day of first study treatment prior to the initiation of study treatment. Women of childbearing potential must agree to use highly effective contraceptive measures from the time of informed consent through 7 months after last dose of study drug. Women of childbearing potential willing to use highly effective contraceptive measures from the time of informed consent through 7 months after last dose of study drug
Exclusion criteria 9
- Left ventricular ejection fraction (LVEF) <53% (Current echocardiography recommendations set low normal value of 2D LVEF as 54% for women and 52% for men and hence in the 2016 EACVI position statement a reduction of LVEF below 53% was classified as abnormal)
- Valvular heart disease
- Previous malignancy requiring treatment with anthracyclines or chest radiotherapy
- A life expectancy of ≤12 weeks
- Currently pregnant (confirmed with positive pregnancy test performed from -7 to -1 days prior to start study drug) or unwilling to adopt highly effective contraceptive method
- Currently breast-feeding women
- History of hypersensitivity to dapagliflozin or any of the excipients of the product
- History of Diabetic Ketoacidosis (DKA) requiring medical intervention (e.g. emergency room visit and/or hospitalization) within 1 month prior to enrolment visit
- Type 1 diabetes mellitus
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- to assess whether the administration of dapagliflozin is associated with a lower rate of asymptomatic and symptomatic CTRCD during 18 months during a 18 months follow-up
Secondary endpoints 1
- to assess whether the administration of dapagliflozin is associated with a lower rate of asymptomatic CTRCD during 18 months
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Forxiga 10 mg film-coated tablets
PRD2437145 · Product
- Active substance
- Dapagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 5.4 g gram(s)
- Max treatment duration
- 18 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BK01 — -
- Marketing authorisation
- EU/1/12/795/007
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- use indication different from the marketing authorization
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fondazione IRCCS Policlinico San Matteo
- Sponsor organisation
- Fondazione IRCCS Policlinico San Matteo
- Address
- Viale Camillo Golgi 19
- City
- Pavia
- Postcode
- 27100
- Country
- Italy
Scientific contact point
- Organisation
- Fondazione IRCCS Policlinico San Matteo
- Contact name
- Laura Scelsi
Public contact point
- Organisation
- Fondazione IRCCS Policlinico San Matteo
- Contact name
- Laura Scelsi
Locations
1 EU/EEA country · 9 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruitment ended | 316 | 9 |
| Rest of world | — | 0 | — |
Investigational sites
Alessandro Manzoni Hospital
UO Cardiologia, Via Dell' Eremo 9, 23900, Lecco
Azienda Unita' Sanitaria Locale Toscana Nord Ovest
Cardiologia, Via Aurelia 335, 55041, Camaiore
Fondazione IRCCS Policlinico San Matteo
SC Cardiologia 1, Viale Camillo Golgi 19, 27100, Pavia
Fondazione IRCCS San Gerardo Dei Tintori
SS Cardiologica Clinica dell'Adulto, Via Giovanni Battista Pergolesi 33, 20900, Monza
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Cardio-oncology and Rare Diseases Unit, Piazzale Carlo Cinelli 4, 61121, Pesaro
IRCCS Istituto Nazionale Tumori Fondazione Pascale
SC Cardiologia, Via Mariano Semmola 52, 80131, Naples
Istituti Clinici Scientifici Maugeri S.p.A. Societa' Benefit In Forma Abbreviata Istituti Clinici Scientifici Maugeri S.p.A. Sb O Anche Ics Maugeri S.p.A. Sb O Maugeri S.p.A. Sb
Cardiologia Riabilitativa, Via Salvatore Maugeri 10, 27100, Pavia
Azienda Unita Sanitaria Locale Di Piacenza
Cardiologia e UTIC, Via Giuseppe Taverna 49, 29121, Piacenza
Istituto Tumori Bari Giovanni Paolo II
Cardiology Unit, Viale Orazio Flacco 65, 70124, Bari
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2024-12-03 | 2024-12-03 | 2026-03-31 |
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.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-518611-18-00 | 6 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_blank | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_CTD authorization | 1 |
| Recruitment arrangements (for publication) | L1_ICF_substudy_2024-518611-18-00_9May2025 | 1 |
| Subject information and informed consent form (for publication) | L1_GP letter | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF other center | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF SanMatteo | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_FORXIGA | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ITA_2024-518611-18-00 | 5 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-16 | Italy | Acceptable 2024-11-12
|
2024-12-03 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-10-14 | Italy | Acceptable 2025-12-15
|
2025-12-17 |