Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent

Status: Recruiting
Location: See all (4) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 4
SUMMARY

Breast cancer is the most commonly cancer in women in the overall global population. According to the World Cancer Research Fund International, there were more than 2.25 million new cases of breast cancer in women in 2020. Although the modern treatment strategies, based on the complex care, which consists of surgery, radiotherapy, hormone therapy, and targeted chemotherapy directed at specific cancer molecules have substantially reduced the risk of death due to breast cancer, their wide adoption results in the wider prevalence of cardiotoxicity, defined as either symptomatic heart failure, or asymptomatic contractile dysfunction. The occurrence of cardiotoxicity induced by anti-cancer therapies is estimated at 5-15%, and its development is the primary cause of therapy termination, which significantly reduces the probability of the efficacy of treatment. Several attempts have been made to determine the efficacious preventive strategy, which could diminish the risk of cancer-therapy induced cardiotoxicity. The results of the prior studies indicated a trend towards lower risk of troponin elevation, or left ventricular contractile dysfunction with the introduction of drugs interfering with the renin-angiotensin-aldosterone (RAA) axis, which constitute the primary treatment modality in heart failure with reduced ejection fraction (HFrEF). Sacubitril/valsartan, the novel therapeutic agent, has been demonstrated to significantly improve prognosis in patients with HFrEF. Prior retrospective, small, single-center studies have shown that treatment with sacubitril/valsartan may reduce the risk of cancer-therapy induced cardiotoxicity, or reverse contractile dysfunction caused by anti-cancer therapy. However, no large randomized data confirmed these findings. Therefore, the Sacubitril/Valsartan in PriMAry preventIoN of the cardiotoxicity of systematic breaST canceR trEAtMent) study, has been designed to verify, whether the preventive use of sacubitril/valsartan administered in the doses recommended in patients with HFrEF in breast cancer patients undergoing adjuvant chemotherapy with anthracyclines or anthracyclines and HER-2 monoclonal antibodies, will reduce the incidence of cardiotoxicity defined as impaired left ventricular systolic function on transthoracic echocardiography (TTE). In the trial, a total of 480 patients with histologically confirmed breast cancer, who are eligible for chemotherapy with anthracyclines or anthracyclines and HER-2 monoclonal antibodies, will undergo 1:1 randomization to either preventive treatment with sacubitril/valsartan or placebo. The patients will be followed for 24 months, and will have repetitive efficacy and safety examinations, including echocardiography, MRI (optionally), electrocardiography including 24-h Holter monitoring, blood tests, functional capacity tests and quality of life assessment.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Healthy Volunteers: f
View:

• Written informed consent

• Female gender, aged 18 years and over

• Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (Estrogen receptor - ER, Progesterone receptor - PR, Human epidermal growth factor receptor 2 - HER2, Kiel - Ki67)

• Ability to take oral medication and willingness to adhere to the planned regimen

• Tumor grade IA-IIIC or oligometastatic grade IV

• Radical treatment plan including surgery

• Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and/or anti-HER2 drugs

• Eastern Cooperative Oncology Group (ECOG) 0-2 general status

• LVEF ≥ 50% as assessed by echocardiography

• Sinus rhythm

Locations
Other Locations
Poland
Maria Sklodowska-Curie Institute - Oncology Centre (MSCI), Gliwice Branch
RECRUITING
Gliwice
Holy Cross Cancer Centre, Cardio-Oncology Division
RECRUITING
Kielce
Regional Cancer Centre in Opole
RECRUITING
Opole
Silesian Center for Heart Diseases
ACTIVE_NOT_RECRUITING
Zabrze
Contact Information
Primary
Mateusz Tajstra, MD, PhD, Assoc Prof
mateusztajstra@wp.pl
+48323733860
Backup
Lucyna Broja
l.broja@sccs.pl
+48323733853
Time Frame
Start Date: 2024-04-17
Estimated Completion Date: 2029-02
Participants
Target number of participants: 600
Treatments
Experimental: Experimental: Sacubitril/Valsartan
After assessment of the tolerance of the drug during the single-blind period, during the which the starting dose of the drug of 100 mg b.i.d. should be increased after two weeks to the target dose 200 mg b.i.d, the patients will be randomized in 1:1 ratio to either intervention or placebo group. In the experimental arm, the patients after randomization will receive the dose 200 mg b.i.d of sacubitril/valsartan for the course of the study. If the patients does not tolerate the target dose of 200 mg b.i.d., the reduction of the drug dose to 100 mg b.i.d. will be possible at the discretion of the physician-in-charge.
Placebo_comparator: Placebo
After assessment of the tolerance of the drug during the single-blind period, during the which the starting dose of the drug of 100 mg b.i.d. should be increased after two weeks to the target dose 200 mg b.i.d, the patients will be randomized in 1:1 ratio to either intervention or placebo group. In the placebo arm, the patients will receive the matching placebo with an identical strategy of dose reduction as in the intervention group, at the discretion of the physician-in-charge.
Related Therapeutic Areas
Sponsors
Collaborators: Medical Research Agency, Poland
Leads: Silesian Centre for Heart Diseases

This content was sourced from clinicaltrials.gov