Potential Protective Role of SGLT-2 Inhibitors for Chemotherapy-induced Cardiotoxicity

NCT06341842 | Recruiting Phase 2

• 1 other identifier: EudraCT 2022-003377-28
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether dapagliflozin reduces chemotherapy-induced cardiotoxicity in participants with breast cancer treated with (neo-)adjuvant Anthracycline-based chemotherapy +/- trastuzumab. The study aims to describe the efficacy for dapagliflozin as compared to standard of care. Participants will be recruited in participating centers, where they are planning on starting (neo-) adjuvant ACT-based chemotherapy and/or trastuzumab for stage I-III breast cancer.

Conditions

Breast Cancer

Keywords

cardiotoxicity; Dapagliflozin; SGLT-2; breast cancer; Anthracycline-based chemotherapy; trastuzumab; Asymptomatic CTRCD; Symptomatic CTRCD; ESC Cardio-Oncology Guidelines

Outcome Measures

Primary Outcomes (1)

• 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.

  Change of Left Ventricular Ejection Fraction Global Longitudinal Strain at 3-6-12 and 18 months compared with baseline will be measured using transthoracic echocardiography.

  baseline, 3 months, 6 months, 12 months and 18 months.

Secondary Outcomes (8)

• Difference in severe, moderate and mild asymptomatic CTRCD between the two groups during 18 months according to the background therapy with AC with or without TZ and with or without the use of any of ACEi, angiotensin receptor blockers, or b-blockers

  baseline, 3 months, 6 months, 12 months and 18 months.

• Difference in symptomatic CTRCD between the two groups during 18 months according to the background therapy with AC with or without TZ (subgroup analysis)

  baseline, 3 months, 6 months, 12 months and 18 months.

• Change from baseline in end diastolic and systolic left ventricular volumes and in left atrial volume during 18 months

  baseline, 3 months, 6 months, 12 months and 18 months.

• Change from baseline of at least of one grade of diastolic disfunction (according to ESC guidelines during 18 months.

  baseline, 3 months, 6 months, 12 months and 18 months.

• Change in plasma levels of the bio-humoral marker NT-pro-BNP between baseline and follow-up

  baseline, 3 months, 6 months, 12 months and 18 months.

Other Outcomes (6)

• Safety Outcomes: TEAE incidence

  baseline, 3 months, 6 months, 12 months and 18 months.

• Toxicity: renal failure evaluation.

  baseline, 3 months, 6 months, 12 months and 18 months.

• Toxicity: hypoglycaemia evaluation

  baseline, 3 months, 6 months, 12 months and 18 months.

Study Arms (2)

Active group - Dapagliflozin 10 mg

EXPERIMENTAL

Drug: Dapagliflozin 10mg Tab

Control group - Standard of care

NO INTERVENTION

Interventions

Dapagliflozin 10mg Tab DRUG

Dapaglifloziin 10 mg 1 tab daily

Also known as: forxiga 10mg

Active group - Dapagliflozin 10 mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 .

You may not qualify if:

• Left ventricular ejection fraction (LVEF) \<53%\*
• 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

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

Related Publications (1)

• Greco A, Quagliariello V, Rizzo G, Tedeschi A, Schirinzi S, Turco A, Galiazzo M, Acquaro M, De Amicis M, Klersy C, Ghio S, Perrone L, Paccone A, Uccello G, Canale ML, Oliva S, Guerra F, De Luca L, Maurea N, Scelsi L. SGLT2i Dapagliflozin in primary prevention of chemotherapy induced cardiotoxicity in breast cancer patients treated with neo-adjuvant anthracycline-based chemotherapy +/- trastuzumab: rationale and design of the multicenter PROTECT trial. Cardiooncology. 2025 Sep 1;11(1):79. doi: 10.1186/s40959-025-00368-9.

  PMID: 40890873 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Cardiotoxicity

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Central Study Contacts

Laura Scelsi, Cardiologist

CONTACT

+390382501326; l.scelsi@smatteo.pv.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Investigator initiated Phase II "proof of concept", multicentre, randomized 1:1, open label, parallel-groups study, designed to evaluate if dapagliflozin reduces chemotherapy induced cardiotoxicity in participants with breast cancer treated with (neo-) adjuvant Anthracycline-based chemotherapy +/- trastuzumab.

Study Record Dates

• First Submitted: March 19, 2024
• First Posted: April 2, 2024
• Study Start: October 19, 2023
• Primary Completion: April 19, 2025
• Study Completion: April 19, 2025
• Last Updated: April 2, 2024

Record last verified: 2024-03

Locations

IT (1)