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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03265574
Recruitment Status : Recruiting
First Posted : August 29, 2017
Last Update Posted : July 17, 2020
Sponsor:
Collaborators:
Newcastle University
University of Durham
Newcastle-upon-Tyne Hospitals NHS Trust
Information provided by (Responsible Party):
South Tees Hospitals NHS Foundation Trust

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
Breast Cancer Non Hodgkin Lymphoma Drug: Enalapril 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: a Phase 3 Randomised, Open Label, Blinded Endpoint, Superiority Trial of Enalapril to Prevent Anthracycline-induced CardioToxicity
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. Cardiac troponin T release [ Time Frame: One month after last dose of anthracycline ]
    Cardiac troponin T release during anthracycline treatment


Secondary Outcome Measures :
  1. Cardiac function [ Time Frame: One month after last dose of anthracycline ]
    Cardiac function assessed by echocardiogram

  2. Adherence to enalapril [ Time Frame: One month after last dose of anthracycline ]
    Ability of participant to adhere to enalapril

  3. Adverse Events / Reactions [ Time Frame: One month after last dose of anthracycline ]
    Number and severity of Adverse Events and Reactions

  4. Anxiety or distress related to trial participation [ Time Frame: One month after last dose of anthracycline ]
    Anxiety or distress related to trial participation

  5. Cancer and chemotherapy outcomes [ Time Frame: One month after last dose of anthracycline ]
    Cancer and chemotherapy outcomes in the population under study

  6. Cardiac troponin I release [ Time Frame: One month after last dose of anthracycline ]
    cardiac troponin I release during anthracyline treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03265574


Contacts
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Contact: David Austin 01642 850850 ext 55909 david.austin@nhs.net
Contact: Vicky Wheeldon 0191 208 5825 PROACT@ncl.ac.uk

Locations
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United Kingdom
South Tees Hospitals NHS FT Recruiting
Middlesbrough, Teesside, United Kingdom, TS4 3BW
Contact: David Austin         
Sponsors and Collaborators
South Tees Hospitals NHS Foundation Trust
Newcastle University
University of Durham
Newcastle-upon-Tyne Hospitals NHS Trust
Investigators
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Study Chair: Vicky Wheeldon Study Chair
  Study Documents (Full-Text)

Documents provided by South Tees Hospitals NHS Foundation Trust:
Informed Consent Form  [PDF] July 24, 2017

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Responsible Party: South Tees Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03265574    
Other Study ID Numbers: 2016152
First Posted: August 29, 2017    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Breast Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases
Enalapril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents