Overview
The purpose of this study is to evaluate the effect of dapagliflozin on the incidence of cancer therapeutics-related cardiac dysfunction in patients with breast cancer receiving anthracycline treatment.
Description
This is a multicentre, randomised, double-blind, placebo-controlled phase III study, evaluating the effect of dapagliflozin versus placebo on prevention of cardiotoxicity in breast cancer patients undergoing anthracycline-based chemotherapy.
Eligibility
Inclusion Criteria:
- Age > 18 years and < 80 years.
- Diagnosis of invasive breast cancer [stage I-III] and planned anthracycline treatment within 60 days.
- Signed Informed Consent to participate in the study.
Exclusion Criteria:
- Urinary tract infection with the need for treatment with an antibiotic 48 hours before the scheduled start of anthracycline treatment.
- Recognised heart failure or symptoms which, in the opinion of the investigator may be a symptom of undiagnosed heart failure.
- Left ventricular ejection fraction < 50% at the time of the screening.
- Severe valvular heart disease.
- A history of clinically significant arrhythmia, including atrial fibrillation regardless of type (at discretion of the investigator).
- A history of stroke.
- Cardiomyopathy: congenital, post-inflammatory, toxic, infiltrative (e.g. amyloidosis, sarcoidosis, haemochromatosis), postnatal or hypertrophic.
- Pulmonary hypertension.
- Uncontrolled arterial pressure or systolic pressure < 80 mmHg at screening (at the discretion of the investigator).
- BMI > 40 kg/m2.
- Diagnosed type 1 or type 2 diabetes or fasting glucose ≥ 126 mg/dl or HbA1C ≥ 6,5% (48 mmol/mol).
- Pregnancy or breastfeeding.
- Lack of compliance to use highly effective method of birth control.
- Expected or possible treatment with epirubicin or liposomal doxorubicin within 12 months.
- Taking another study drug or drugs from the group of SGLT2 inhibitors up to 6 months before the screening visit.
- Taking semaglutide, liraglutide and metformin during the 30 days preceding the screening visit.
- eGFR < 25 ml/min/1.73m2 according to CKD EPI.
- Life expectancy < 12 months or cancer disease stage IV according to the TNM classification.
- Alanine transaminase or aspartate transaminase levels above 2.5 times the local norm.
- Anemia with Hemoglobin < 9 g/dl.
- Kidney failure > G2 (according to KDIGO classification).
- Liver disorders, Child-Pugh score > 4.
- Known, active infections with HIV, HBV, HCV, tuberculosis.
- Any other condition which, in the opinion of the investigator, makes it impossible to fulfill the requirements for participation in this study.