Clinical trial NCT06304857: CardioPROTECTion with Dapagliflozin in Breast Cancer Patients Treated with AnthrAcycline - PROTECTAA TRIAL
Official title: A Multicentre, Randomised, Double-blind, Placebo-controlled Phase III Study, Evaluating the Effect of Dapagliflozin on Prevention of Cardiotoxicity in Breast Cancer Patients Undergoing Anthracycline-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Heart Failure
Keywords: breast cancer
heart failure
ejection fraction
anthracyclines
Lead sponsor: 4th Military Clinical Hospital with Polyclinic, Poland
Sponsor class: OTHER
First posted: 2024-03-12
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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 criteria: 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.

Primary outcomes:
measure: Primary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 12 months.
timeFrame: 12 months
Secondary outcomes:
measure: Secondary efficacy composite endpoint (cancer therapeutics related cardiac dysfunction) at 6 months.
timeFrame: 6 months
measure: Change in left ventricular ejection fraction at 6 and 12 months.
timeFrame: 6 and 12 months
measure: Change in left ventricular diastolic function at 6 and 12 months.
timeFrame: 6 and 12 months
measure: Change in Troponin I after 6 and 12 months.
timeFrame: 6 and 12 months
measure: Change in NTproBNP levels at 6 and 12 months.
timeFrame: 6 and 12 months
measure: Quality of life at 6 and 12 months assessed using the five-dimensional EQ-5D questionnaire.
timeFrame: 6 and 12 months
measure: Occurrence of death from any cause.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Composite endpoint of cardiovascular events.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of death from any cardiovascular reasons.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of non-fatal myocardial infarction.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of non-fatal stroke.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of hypoglycaemia.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of ionic disorders.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of renal failure.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of hypersensitivity to investigated drug.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of allergic reactions.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
measure: Occurrence of infection.
timeFrame: 13 months (additional 1 month of safety follow-up after end of treatment).
Other outcomes:
Locations:
city: Wrocław
country: Poland
facility: 4th Military Clinical Hospital with Polyclinic
state: Dolnośląskie
city: Wrocław
country: Poland
facility: Lower Silesian Centre for Oncology, Lung Diseases and Hematology
state: Dolnośląskie
city: Warsaw
country: Poland
facility: Military Medical Institute
state: Mazowieckie
Study officials:
affiliation: 4th Military Clinical Hospital with Polyclinic
name: Waldemar Banasiak, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: