Prevention of cardiotoxicity MedDRA version: 20.0 Level: PT Classification code 10048610 Term: Cardiotoxicity System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: Enalapril Maleate
Product Code: Enalapril
Pharmaceutical Form: Tablet
INN or Proposed INN: Enalapril Maleate
CAS Number: 76095-16-4
Current Sponsor code: Enalapril
Other descriptive name
Sponsors
South Tees NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adult patients with histopathologically* confirmed breast carcinoma who have received surgery for their breast cancer; • Planned to receive 6 cycles of EC 90 (total planned dose 540 mg/m2 epirubicin) or FEC 75 (total planned dose 450 mg/m2 epirubicin) adjuvant chemotherapy regimen; OR • Adult patients with histopathologically confirmed non-Hodgkin lymphoma planned to receive 6 cycles of R-CHOP or CHOP (total planned dose 300mg/m2 doxorubicin) chemotherapy AND • Written informed consent. *Patients with HER2+ breast cancer are eligible for inclusion. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 85 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 85
Exclusion criteria
Exclusion criteria: • Positive baseline cardiac troponin T (=14ng/L); • known contraindication to ACE inhibitor e.g. renal artery stenosis, severe aortic stenosis; • are taking, or have a previous intolerance to ACEI (e.g. angioedema); • patient already taking other agents acting on the renin-angiotensin-aldosterone system e.g. Aliskiren, angiotensin receptor blockers (ARBs), Entresto (sacubitril/valsartan), spironolactone, eplerenone; • LVEF 160/100mmHg**, or ambulatory BP of 150/95mmHg); • previous myocardial infarction; • known metastatic breast cancer; • previous exposure to anthracycline chemotherapy; • are pregnant or breastfeeding; • previous Herceptin treatment or planned Herceptin treatment within four weeks following anthracycline chemotherapy; • for patients of childbearing potential: refusal to use adequate contraception throughout the trial;*** • any other invasive cancer diagnosed and treated in the past 5 years; • symptomatic or severe asymptomatic radiation-induced cardiac disease; • participation in other interventional medicinal trials in the past 6 months; • judgement by the investigator that the patient has a prognosis of < 1 year or are unlikely to complete 6 cycles of chemotherapy. • judgement by the investigator that the patient is high risk for tumour lysis syndrome (applicable only to NHL patients). • judgement by the Investigator that the patient should not participate in the study, for example, if the patient is unlikely to comply with study procedures, restrictions, and requirements. *<50% as defined by Simpson’s biplane method; if absolute measurements are not possible, then a visually normal assessment of LVEF is acceptable for inclusion. **White coat hypertension is more common, and should be ruled out by an ambulatory blood pressure monitor ***Female patients between the ages of 18 and 50 will receive a pregnancy test at baseline. Adequate methods of contraception are those that can achieve a failure rate of less than 1% per year when used consistently and correctly, such methods include: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation o oral o intravaginal o transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation o oral o injectable o implantable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomy/vasectomised partner • true sexual abstinence (refraining from heterosexual intercourse during the entire period of study treatment)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To understand if a commonly used heart drug called enalapril can stop patients who are receiving chemotherapy for their breast cancer or non-Hodgkin lymphoma from getting heart damage. This will be measured by testing blood samples taken and comparing the levels of a marker in the blood (called troponin T).;Secondary Objective: Secondary objectives will concentrate on understanding the effectiveness of enalapril in preventing cardiotoxicity. They include important measures of heart function which relate directly to patients: • heart function will be assessed by heart scans (called echocardiograms), at baseline and following completion of chemotherapy; • presence or absence of markers in the blood (called cardiac troponin I) at any time during chemotherapy and one month after the last dose of chemotherapy; • whether patients take the enalpril as prescribed; • side effects of enalapril; • any anxiety or distress related to trial participation. ;Primary end point(s): The primary outcome of PROACT is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and one month after the last dose of anthracycline.;Timepoint(s) of evaluation of this end point: Any time during anthracycline treatment and one month after the last dose of anthracycline. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary outcomes will focus on the effectiveness of enalapril in preventing cardiotoxicity. These include important measures of cardiac function which relate directly to patient outcomes: • cardiac function assessed by echocardiogram, including global longitudinal strain (GLS), and measurements of left ventricular ejection fraction (LVEF), at baseline and following completion of anthracycline chemotherapy; • cardiac troponin I release at any time during adjuvant chemotherapy and one month after the last dose of epirubicin; • adherence to enalapril; • side effects of enalapril; • adverse events; • any anxiety or distress related to trial participation. ;Timepoint(s) of evaluation of this end point: Cardiac function by echocardiogram will be assessed 4 weeks after the final cycle of chemotherapy. Cardiac troponin levels will be assessed at day 1 of each cycle from the second cycle of chemotherapy until study completion (4 weeks following the last cycle of chemotherapy. Adherence, adverse event reporting and general patient safety assessments will take place from first drug intake, at each titration visit and day 1 of each cycle until the trial completion visit (4 weeks after completion of chemotherapy). | — |
Countries
United Kingdom
Contacts
Public ContactRobbie Brown
Newcastle Clinical Trials Unit
Outcome results
None listed