PROACT: Can we Prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?

• Status: Recruiting
• Trial end date: 2021-09-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: South Tees Hospitals NHS Foundation Trust
• Collaborators: Newcastle University; Newcastle-upon-Tyne Hospitals NHS Trust; University of Durham
• Treatments: Enalapril; Enalaprilat

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