AzTrials
AzTrials

Breast CancerPhase 3PROACTNCT03265574

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

A Phase 3 study testing Enalapril in people with Breast Cancer and Non Hodgkin Lymphoma, run by South Tees Hospitals NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Non Hodgkin Lymphoma
What is being tested?
Enalapril
Could I receive a placebo?
No, everyone receives an active treatment
How many people
111 participants
Where
1 siteUnited Kingdom
Study dates
4 Oct 2017to 4 Aug 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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**
  • Patients with HER2+ breast cancer are eligible for inclusion. ** Patients who will receive an alternative anti-CD20 monoclonal antibody are eligible (for example O-CHOP), as long as the total planned doxorubicin dose is ≥300mg/m2 over 6 cycles

Who cannot join

  • 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;
Show all 37Show fewer
  • 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;
  • 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;
  • 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
  • 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
  • true sexual abstinence

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • South Tees Hospitals NHS FT

    Middlesbrough, Teesside, TS4 3BW

Other trials in United Kingdom

About this study

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

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.

Read the 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.

Being tested
Enalapril
Medical subject headings
Breast Neoplasms, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnalaprilDrug

    Enalapril is an Angiotensin Converting Enzyme (ACE) inhibitor which supresses the reninangiotensin-aldosterone system resulting in increased plasma renin activity and decreased aldosterone secretion

Study groups in NCT03265574
Study groupRoleWhat they receive
InterventionExperimentalNot described
Receives: Drug: Enalapril
Standard careNo interventionNot described

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cardiac troponin T release

    Cardiac troponin T release during anthracycline treatment

    Measured: One month after last dose of anthracycline

Secondary outcomes (6)

  1. Cardiac function

    Cardiac function assessed by echocardiogram

    Measured: One month after last dose of anthracycline

  2. Adherence to enalapril

    Ability of participant to adhere to enalapril

    Measured: One month after last dose of anthracycline

  3. Adverse Events / Reactions

    Number and severity of Adverse Events and Reactions

    Measured: One month after last dose of anthracycline

  4. Anxiety or distress related to trial participation

    Anxiety or distress related to trial participation

    Measured: One month after last dose of anthracycline

  5. Cancer and chemotherapy outcomes

    Cancer and chemotherapy outcomes in the population under study

    Measured: One month after last dose of anthracycline

  6. Cardiac troponin I release

    cardiac troponin I release during anthracyline treatment

    Measured: One month after last dose of anthracycline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2017
  2. Study start4 Oct 2017
  3. Primary completion4 Aug 2023
  4. Study completion4 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
111 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03265574
Sponsor's protocol ID
2016152
Acronym
PROACT
Status last verified
Feb 2024
First submitted
24 Aug 2017
Last updated
20 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Austin D, Maier RH, Akhter N, Sayari M, Ogundimu E, Maddox JM, Vahabi S, Humphreys AC, Graham J, Oxenham H, Haney S, Cresti N, Verrill M, Osborne W, Wright KL, Goranova R, Bailey JR, Kalakonda N, Macheta M, Kilner MF, Young ME, Morley NJ, Neelakantan P, Gilbert G, Thomas BK, Graham RJ, Fujisawa T, Mills NL, Hildreth V, Prichard J, Kasim AS, Hancock HC, Plummer C. Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial. JACC CardioOncol. 2024 Aug 27;6(5):684-696. doi: 10.1016/j.jaccao.2024.07.010. eCollection 2024 Oct.

    PubMed 39479329

  • Maier RH, Plummer C, Kasim AS, Akhter N, Ogundimu E, Maddox J, Graham J, Stewart M, Wardley A, Haney S, Vahabi S, Oxenham H, Humphreys A, Cresti N, Verrill M, Graham R, Chang L, Hancock HC, Austin D. Preventing cardiotoxicity in patients with breast cancer and lymphoma: protocol for a multicentre randomised controlled trial (PROACT). BMJ Open. 2022 Dec 30;12(12):e066252. doi: 10.1136/bmjopen-2022-066252.

    PubMed 36585130

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Enalapril in people with Breast Cancer and Non Hodgkin Lymphoma, run by South Tees Hospitals NHS Foundation Trust at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cardiac troponin T release (time frame: One month after last dose of anthracycline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03265574, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in