Condition category
Cancer
Date applied
26/04/2018
Date assigned
13/05/2018
Last edited
14/08/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Breast cancer is one of the most common cancers. In the UK 150 people per day are diagnosed. Often breast cancer is treated with anti-cancer drugs, called chemotherapy. Anthracyclines are a type of chemotherapy often used to treat breast cancer and are very effective. However, as with all drugs anthracyclines come with side effects. Heart damage is the most serious side effect. Heart damage can happen at the time of treatment, but symptoms only develop much later. Detecting heart damage relies on heart scans (called echocardiography, or echo for short). The usual measurements can only identify heart damage when it is already established. Waiting until damage is established means a reduced chance of heart recovery. Unfortunately, anthracycline heart damage can sometimes be severe and affect length and quality of life. Doctors and patients need better ways of detecting heart damage earlier. This study aims to understand if new echo measurements can be used to detect heart side effects sooner. It is not yet known whether these new measurements are better than what is currently done. Some patients are already involved in a linked study called PROACT. These patients have already given their permission for echo studies and analysis. The plan is to ask another group of patients receiving chemotherapy as part of standard care but not currently in PROACT, to participate in this study, called the PROACT PLUS registry.

Who can participate?
Patients aged 18 and over with breast cancer who are going to receive anthracycline-based treatment

What does the study involve?
There are no additional treatments involved in this study, but patients undergo additional echo scans and blood tests (called troponin). The additional echo analysis is performed on normal echo pictures and is called the PROACT echo sub-study. The plan is to follow up the registry patients for 18 months and to combine the information from both trial and registry groups to answer the study questions.

What are the possible benefits and risks of participating?
The benefit to participants is additional heart monitoring that is not routine for all breast cancer patients undergoing treatment with anthracyclines. Patients studied in the registry will be receiving anthracycline-based chemotherapy and/or Herceptin as part of their routine cancer care. The risks and burdens posed on patients from taking these drugs include: nausea, vomiting, tiredness, low white cell count, infection, diarrhoea, and abdominal or joint pains. Participation in the registry does not pose any major risks to patients due to the observational nature of the study. Furthermore no study-specific medication will be given to patients during this period. Blood sample taking could cause some discomfort and distress for patients. There is a very small risk of infection or bleeding at the site of blood taking but the risks of these are extremely small and rare. Where possible, study blood samples will be taken alongside samples taken for routine care. Echocardiography may cause some discomfort at the probe site due to some pressure used when taking the images. No radiation risk is involved in taking the scans.

Where is the study run from?
South Tees NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
June 2018 to June 2021

Who is funding the study?
South Tees Research and Development Fund (UK)

Who is the main contact?
Dr Sharareh Vahabi
sharareh.vahabi@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Dr Sharareh Vahabi

ORCID ID

http://orcid.org/0000-0002-6683-6105

Contact details

South Tees NHS Foundation Trust
The James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
+44 (0)1642 850850
sharareh.vahabi@nhs.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Version 1.0

Study information

Scientific title

PROACT PLUS Registry and Echocardiographic sub-study: an observational, prospective, cohort study assessing the use of novel echocardiographic tools and measurement of troponin to help detect early signs of cardiotoxicity in patients treated for breast cancer

Acronym

PROACT PLUS Registry and Echo Sub-study

Study hypothesis

Can we detect early signs of cardiotoxicity using novel echocardiography measurements and heart specific blood tests?

Ethics approval

HRA and Health and Care Research Wales (HCRW), 14/08/2018, REC ref: 18/EM/0177

Study design

Multicentre observational prospective cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Breast cancer

Intervention

PROACT PLUS registry and echo-substudy is a multicentre, observational, prospective cohort study assessing the use of novel echocardiographic tools and measurement of troponin to help detect early signs of cardiotoxicity. This registry is complimentary to the NIHR-funded PROACT clinical trial which is currently ongoing in the Northeast of England. PROACT (PRevention Of Anthracycline Cardiovascular Toxicity in patients treated for breast cancer, PB-PG-0815-20061, NCT03265574, IRAS ID 213348) is a multicentre, phase 3, randomised, open label, blinded endpoint study that aims to assess the effectiveness of enalapril in preventing cardiotoxicity in patients with newly diagnosed breast cancer requiring anthracycline based chemotherapy. One hundred and seventy patients, in whom high-dose anthracycline chemotherapy is planned will be randomised to either usual care plus enalapril or usual care. The primary end point is the presence of detectable troponin T (14ng/L or greater), measured at the end of each chemotherapy cycle and 4 weeks after chemotherapy. As part of the assessment of key secondary endpoints in the trial, transthoracic echocardiography will be performed at two time points using a standardised British Society of Echocardiography (BSE) template: prior to commencing chemotherapy, and 1 month after the completion of anthracycline chemotherapy. Trial echocardiographic secondary endpoints include the established measures of LVEF and global longitudinal strain (GLS).

The PROACT PLUS registry includes adult patients with newly diagnosed breast cancer who are planned to receive anthracyclines either in an adjuvant or neo-adjuvant setting for their treatment. Patients will not be eligible for inclusion in the registry if they meet the inclusion criteria for the PROACT clinical trial or have metastatic breast cancer. Therefore, the PROACT PLUS registry is complementary to the PROACT clinical trial and eligibility for trial or registry is mutually exclusive. The aim is to include 85 patients, which will be the same number as a single arm in the PROACT trial. A patient information sheet will be provided and any uncertainties about the registry raised by the patient will be addressed. After all questions are answered, the patient will be asked to sign the consent form to confirm participation.

Once patient has agreed to participate they will undergo a series of assessments during their treatment as described below:
1. Review of medical history
2. Height and weight measurement
3. Blood pressure and heart rate
4. Blood samples for troponin measurement (prior to each chemotherapy cycle, 4 weeks and 12 months after the last dose of anthracyclines)
5. Blood samples for future research (prior to cycle 1, 3 and 5 and 4 weeks and at least 12 months after the last dose of anthracyclines)
6. Heart scan (echocardiogram) at baseline, 4 weeks and 12 months after anthracyclines
7. Cheek swab for DNA analysis (optional): will be done once only during the registry period

No study specific drugs will be given to patients in the registry. The assessments in the registry will mirror the assessments in the PROACT clinical trial to allow a direct comparison of patients within and in both groups. The combined PROACT trial and PROACT PLUS registry data obtained from this cohort of patients with breast cancer will help inform the future of cardiovascular care in patients treated with anthracyclines and can lead to further useful research in the field of cardio-oncology.

Intervention type

Other

Phase

Drug names

Primary outcome measure

The presence (≥14ng/L) or absence of cardiac troponin T (<14ng/L) release at any time during anthracycline treatment, 1 month and 12 months after the last dose of anthracycline:
1. Cardiac troponin I release during, 1 month and 12 months after the last dose of anthracyclines
2. Cardiac function assessed by echocardiogram, including GLS, measurement of LVEF, and measurement of novel echocardiographic strain parameters (namely: Global Radial Strain (GRS), Global Circumferential Strain (GCS), torsion and twist, Right Ventricular Free Wall (RVFW), left and right atrial strain), at baseline, 4 weeks following completion of chemotherapy and at 12 months

Secondary outcome measures

There are no secondary outcome measures

Overall trial start date

01/06/2018

Overall trial end date

01/06/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adult patients with a new diagnosis of histopathologically confirmed breast carcinoma
2. Age ≥ 18
3. Planned to receive anthracycline based treatment (adjuvant or neoadjuvant) – any dose
4. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

85

Participant exclusion criteria

1. Meets eligibility criteria for the PROACT trial*
2. Known metastatic breast cancer
*Patients who are otherwise eligible for the PROACT trial will not be eligible to participate in the PROACT registry

Recruitment start date

01/06/2018

Recruitment end date

01/01/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

South Tees NHS Foundation Trust
The James Cook University Hospital Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Sponsor information

Organisation

South Tees NHS Foundation Trust

Sponsor details

The James Cook University Hospital
South Tees Institute for Learning
Research and Innovation
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

South Tees Research and Development Fund

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The protocol is not published online but will be made available to individuals upon request. At the end of the research study a summary sheet/letter outlining all the relevant findings will be disseminated to individuals participated with reference to where they can find information about the results and publications related to the study. An interim and final data analysis will be carried out with planned publication in high-impact peer reviewed journals. The results will also make up a part of a MD thesis. The results will be available around a year after the initial analysis which will be January 2021 and a year after the overall trial end date which will be in June 2022.

IPD sharing statement
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication. There are no plans to disseminate any results that include identifiable personal data. Data will be fully anonymised prior to publication, with all identifiable data removed. Results will be presented in aggregated form in publications.

Intention to publish date

01/06/2022

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

14/08/2018: Ethics approval details added.