Overview

Prevention of Cardiac Dysfunction During Breast Cancer Therapy

Status:
Recruiting
Trial end date:
2025-09-14
Target enrollment:
0
Participant gender:
Female
Summary
Breast cancer is the most common cancer among women. The modern post-surgery treatment with chemotherapy, immunotherapy, radiation and hormone therapy has improved the overall 5-years survival drastically. However, an unwanted effect of the post-surgery treatment is its potentially deleterious effect on the heart resulting in cardiac dysfunction. Angiotensin antagonists are used as part of the heart failure treatment. In smaller studies angiotensin antagonists have shown to have a cardioprotective effect during breast cancer treatment. Sacubitril/valsartan is a potent drug that in addition to an angiotensin antagonist contains a neprilysin inhibitor. Sacubitril/valsartan has proved to be superior to enalapril in chronic heart failure. In this randomized placebo controlled double blind trial we hypothesize that sacubitril/valsartan used concomitantly during anthracycline containing chemotherapy for breast cancer treatment prevents cardiac dysfunction as measured by cardiac magnetic resonance imaging (CMR). PRADA II is a Norwegian multicenter trial intending to recruit 214 patients and follow them for 18 months with CMR, cardiac ultrasound, blood samples, functional capacity tests and health related quality of life questionnaires.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Torbjorn Omland
Collaborators:
Helse Stavanger HF
Klinbeforsk
Norwegian Cancer Society
Novartis
Oslo University Hospital
St. Olavs Hospital
University Hospital of North Norway
University Hospital, Akershus
Treatments:
LCZ 696
Valsartan
Criteria
Inclusion Criteria:

- Women with histological evidence of invasive early breast cancer scheduled for
adjuvant therapy with anti-cancer regimens that include anthracyclines

- Eastern Cooperative Oncology Group performance status 0-1

- Sinus rhythm

Exclusion criteria:

- Age <18 years

- Renal failure, i.e. serum creatinine greater than 133 mol/L (1.5mg/dL) or estimated
glomerular filtration rate (eGFR) < 45 mL/min/1.73m2

- Hyperkalemia, i.e. serum potassium greater than 5.0 mmol/L

- Systolic blood pressure < 100 mgHg

- Uncontrolled hypertension

- Acute myocardial infarction within the last three months

- Contraindication to ACEI or ARB or sacubitril/valsartan, including previous
hypersensitivity reaction, angioedema and renal artery stenosis

- ACEI, ARB, aldosterone antagonist or sacubitril/valsartan use within 4 weeks of study
start

- Clear indication for ACEI, ARB, aldosterone antagonist or sacubitril/valsartan
therapy, including symptomatic heart failure

- History of hemodynamically significant valvular disease

- Active liver disease, i.e. alanine aminotransferase or aspartate aminotransferase
greater than 1.5 times the upper limit of normal

- Participation in another pharmaceutical clinical trial of an investigational medicinal
product (IMP) less than 4 weeks prior to inclusion or use of other investigational
drugs within 5 halflives of enrollment, whichever is longer

- Conditions that would affect the participants to comply with the study protocol as
psychiatric or mental disorders, alcohol abuse or other substance abuse, suspected
poor drug compliance, language barriers or other factors

- Contraindication or inability to undergo CMR examination

- Fertile women with inadequate birth control, pregnancy, and/or breastfeeding. Adequate
contraception includes oral, injected or implanted hormonal methods of contraception,
placement of an intrauterine device or system, vasectomized partner or sexual
abstinence. Fertile women are defined as following menarche and until becoming
postmenopausal unless permanently sterile. A postmenopausal state is defined as no
menses for 12 months without an alternative medical cause

- Life expectancy < 12 months