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

Breast Cancer Clinical Trial

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

Status Not yet recruiting

Clinical Trial 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 cardiac magnetic resonance imaging (MRI). 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, electrocardiography including 24-h Holter monitoring, blood tests, functional capacity tests and quality of life assessment.

Clinical Trial Description

n/a

Related Conditions & MeSH terms

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin Receptor Antagonists
• Breast Cancer
• Breast Diseases
• Breast Neoplasms
• Cancer, Therapy-Related
• Cardiac Toxicity
• Cardiotoxicity
• Heart Failure
• Molecular Mechanisms of Pharmacological Action
• Neoplasm, Breast
• Neoplasms, Second Primary
• Sacubitril/Valsartan

• NCT number: NCT05465031
• Study type: Interventional
• Source: Silesian Centre for Heart Diseases
• Contact: Mateusz Tajstra, MD, PhD, Associate Professor
• Phone: +48323733860
• Email: mateusztajstra@wp.pl
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: February 2023
• Completion date: February 2028