PROACT: Can we Prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?
Study Details
Study Description
Brief Summary
PROACT will establish the effectiveness of the angiotensin-converting enzyme inhibitor (ACEI) enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin lymphoma undergoing adjuvant epirubicin-based chemotherapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
PROACT is a phase 3 randomised, open label, blinded endpoint, superiority trial of enalapril to prevent anthracycline-induced in patients treated for breast cancer and lymphoma.
Anthracyclines used in the treatment of breast cancer cause damage to heart muscle cells; this results in cell death (cardiotoxicity). In UK contemporary practice, epirubicin is the most frequently used anthracycline.
Patients due to receive adjuvant anthracycline chemotherapy (planned epirubicin dose
300mg/m2) for breast cancer at four specialist centres in the North of England will be invited to participate. 170 eligible patients will be randomised in a 1:1 ratio, to either enalapril plus usual care or to usual care. Enalapril will be commenced prior to the first anthracycline dose, titrated to a maximum tolerated dose, and continued during chemotherapy. Chemotherapy will continue per usual care; typically six treatment cycles. Patients will have a blood test performed at the end of each chemotherapy cycle to measure cardiac troponin, and at one month following the last epirubicin dose. Investigators and patients will be blinded to the troponin results. Patients will have an echocardiogram at baseline and following their chemotherapy; they will be assessed in a blinded manner by a central Core Laboratory.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intervention
|
Drug: Enalapril
Enalapril is an Angiotensin Converting Enzyme (ACE) inhibitor which supresses the reninangiotensin-aldosterone system resulting in increased plasma renin activity and decreased aldosterone secretion
|
| No Intervention: Standard care
|
Outcome Measures
Primary Outcome Measures
- Cardiac troponin T release [One month after last dose of anthracycline]
Cardiac troponin T release during anthracycline treatment
Secondary Outcome Measures
- Cardiac function [One month after last dose of anthracycline]
Cardiac function assessed by echocardiogram
- Adherence to enalapril [One month after last dose of anthracycline]
Ability of participant to adhere to enalapril
- Adverse Events / Reactions [One month after last dose of anthracycline]
Number and severity of Adverse Events and Reactions
- Anxiety or distress related to trial participation [One month after last dose of anthracycline]
Anxiety or distress related to trial participation
- Cancer and chemotherapy outcomes [One month after last dose of anthracycline]
Cancer and chemotherapy outcomes in the population under study
- Cardiac troponin I release [One month after last dose of anthracycline]
cardiac troponin I release during anthracyline treatment
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Written informed consent.
-
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 540mg/m2 epirubicin) or FEC 75 (total planned dose 450mg/m2 epirubicin) adjuvant chemotherapy regimen. Patients with HER2+ breast cancer are eligible for inclusion.
OR • Adult patients with histopathologically confirmed non-Hodgkin lymphoma (NHL), planned to receive 6 cycles of R-CHOP or CHOP (total planned dose 300mg/m2 doxorubicin) chemotherapy
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 <50%*;
-
estimated GFR < 30 mL/min/1.73m2 at baseline;
-
hyperkalaemia defined as serum potassium ≥5.5mmol/L;
-
symptomatic hypotension, or Systolic Blood Pressure <100mmHg;
-
poorly-controlled hypertension (Blood Pressure >160/100mmHg**, or ambulatory BP of 150/95mmHg);
-
previous myocardial infarction;
-
known metastatic breast cancer;
-
previous exposure to anthracycline chemotherapy;
-
are pregnant or breastfeeding
-
Herceptin planned treatment within four weeks following anthracycline chemotherapy
-
for patients of childbearing potential: refusal to use adequate contraception throughout the trial;***
-
any other cancer diagnosis;
-
judgment 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
-
oral
-
intravaginal
-
transdermal
-
progestogen-only hormonal contraception associated with inhibition of ovulation
-
oral
-
injectable
-
implantable
-
intrauterine device (IUD)
-
intrauterine hormone-releasing system (IUS)
-
bilateral tubal occlusion
-
vasectomy/vasectomised partner
-
double-barrier contraception (condom and occlusive cap e.g., diaphragm or cervical cap with spermicide)
-
true sexual abstinence
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | South Tees Hospitals NHS FT | Middlesbrough | Teesside | United Kingdom | TS4 3BW |
Sponsors and Collaborators
- South Tees Hospitals NHS Foundation Trust
- Newcastle University
- University of Durham
- Newcastle-upon-Tyne Hospitals NHS Trust
Investigators
- Study Chair: Vicky Wheeldon, Study Chair
Study Documents (Full-Text)
More Information
Publications
None provided.- 2016152