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Trial Title:
Safety of Withdrawal of Pharmacological Treatment for Recovered HER2 Targeted Therapy Related Cardiac Dysfunction
NCT ID:
NCT05880160
Condition:
Cardiotoxicity
HER2-positive Breast Cancer
Heart Failure
Cancer, Therapy-Related
Conditions: Official terms:
Neoplasms, Second Primary
Heart Failure
Cardiotoxicity
Conditions: Keywords:
Cardiotoxicity
HER2-positive Breast Cancer
Heart Failure
Cancer, Therapy-Related
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Two centre open label randomised control trial to evaluate the phased withdrawal versus
continuation of heart failure treatment for 'recovered' human epidermal growth factor
receptor 2 (HER2) therapy-related cardiac dysfunction in non-high risk patients following
completion of HER2 therapy.
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
Open label
Intervention:
Intervention type:
Other
Intervention name:
Phased withdrawal of heart failure medications
Description:
As per arm/group description
Arm group label:
Treatment Withdrawal
Summary:
Breast cancer is the most common cancer in the United Kingdom (UK), but improvements in
treatment mean 3 in 4 people survive for more than 10 years. Many people receive
treatments called human epidermal growth factor receptor 2 (HER2) targeted therapies for
their breast cancer, however these can affect heart function. This 'cardiotoxicity' is
generally temporary and mild, but patients receive drugs to help their heart recover.
Currently it is not known how long patients should receive these treatments. Patients
with other types of heart failure are treated lifelong, but this may not be necessary
here as the damaging cancer drugs have stopped. Taking drugs for many years can have an
impact on people's quality of life, particularly for young patients. It is therefore
important to understand the best treatment length. The investigators will study people
whose heart function has recovered after HER2 therapy heart problems and are not at high
risk for heart disease. The investigators will carefully stop their heart drugs whilst
monitoring them closely with special heart scans and blood tests to detect problems
early. The investigators will also study how patients are currently treated using
national data. The results of this study will help doctors better guide breast cancer
survivors about treatment of heart damage from HER2 cancer therapies.
Detailed description:
Trial design: Two centre open label randomised control trial to evaluate the phased
withdrawal versus continuation of heart failure treatment for 'recovered' human epidermal
growth factor receptor 2 (HER2) therapy-related cardiac dysfunction in non-high risk
patients following completion of HER2 therapy. The trial will include cardiovascular
magnetic resonance scans (CMR) with automated in-line analytics to improve the
sensitivity for detection of early relapse, and detailed patient questionnaires assessing
medication disutility to better understand participant motivations and concerns related
to treatment continuation and withdrawal.
Trial population: The trial will recruit 90 adult participants (>18 years) with a prior
diagnosis of HER2-targeted therapy related cardiac dysfunction, who currently receive
standard heart failure/ cardioprotective medications (any combination of
Angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs]
and/or beta-blockers), and whose cardiac function has 'recovered'. 'Recovery' is defined
as absence of heart failure symptoms with left ventricular ejection fraction (LVEF)
improved to 50% or greater and N-terminal pro B-type natriuretic peptide (NTproBNP)
<200ng/L, for greater than 6 months. Patients will be recruited from Barts Health and
University College London Hospitals (UCLH) cardio-oncology and breast cancer clinics.
Exclusion criteria: Patients with advanced/ metastatic HER2 positive breast cancer
requiring ongoing HER2 therapies or with life expectancy <12months will be excluded.
Patients classed as high/very high cardiotoxicity risk according to the European Society
of Cardiology/International Cardio-Oncology Society Position Statement (Lyon et al,
2020), LVEF <50% prior to HER2-therapies or on completion of anthracycline treatment, or
indications for ongoing ACE inhibitors, ARBs and/or beta-blockers, nor those with
absolute contraindications to CMR.
Interventions and Duration of treatment: Participants will undergo phased withdrawal of
heart failure/ cardioprotective treatments according to a pre-specified algorithm based
on the 'Withdrawal of pharmacological treatment for heart failure in patients with
recovered dilated cardiomyopathy' (TRED-HF) study protocol (Halliday et al 2019). This
had been designed following extensive consultation with independent experts and attempts
to mimic 'real-world' medication withdrawal in clinical practice. Medications will be
down titrated in a phased process every 2 weeks over a maximum of 16 weeks. Drug doses
will be reduced by 50% in a stepwise manner every 2 weeks, until the patient is taking
25% or less of the maximum recommended dose at which point the medication will be
stopped. Monitoring with fortnightly virtual consultations will confirm drug dose
reduction and provide support. Participants will undergo clinical assessment at 6, 14 and
24 weeks and 6, 9 and 12 months with weight, blood pressure, and biomarker measurement.
At baseline, 6- and 12-month visits detailed cardiovascular phenotyping using CMR and
symptom and disutility questionnaires will be undertaken.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Adult participants (>18 years)
2. A prior diagnosis of human epidermal growth factor receptor 2 (HER2)- targeted
therapy related cardiac dysfunction, who currently receive standard heart
failure/cardioprotective medications (any combination of angiotensin-converting
enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs] and/or beta-blockers).
3. Cardiac function has 'recovered'. 'Recovery' is defined as absence of heart failure
symptoms with left ventricular ejection fraction (LVEF) improved to 50% or greater
and N-terminal pro B-type natriuretic peptide (NTproBNP) <125ng/L, for greater than
6 months.
Exclusion Criteria:
1. Advanced/ metastatic HER2 positive breast cancer requiring ongoing HER2 therapies or
with life expectancy <12months.
2. Patients classed as high/very high cardiovascular risk according to the
International Cardio-Oncology Society (ICOS) risk stratification
3. Patients with LVEF <50% prior to HER2-therapy initiation or on completion of
anthracycline treatment
4. Patients with ongoing indications for the cardioprotective medication - ACE
inhibitors, ARBs and/or beta-blockers
5. Patients with absolute contraindications to cardiovascular magnetic resonance scans
(CMR).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
St Bartholemew's Hospital
Address:
City:
London
Zip:
EC1A 7BE
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Benjamin Dowsing, MBBS MSc BSc
Phone:
+447912148972
Email:
benjamin.dowsing@nhs.net
Investigator:
Last name:
Charlotte Manisty
Email:
Principal Investigator
Investigator:
Last name:
Benjamin Dowsing
Email:
Sub-Investigator
Facility:
Name:
University College London Hospital
Address:
City:
London
Zip:
NW1 2BU
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Benjamin Dowsing, MBBS MSc BSc
Phone:
07912148972
Email:
benjamin.dowsing@nhs.net
Investigator:
Last name:
Malcolm Walker
Email:
Principal Investigator
Investigator:
Last name:
Benjamin Dowsing
Email:
Sub-Investigator
Start date:
July 14, 2023
Completion date:
September 2025
Lead sponsor:
Agency:
University College, London
Agency class:
Other
Collaborator:
Agency:
British Heart Foundation
Agency class:
Other
Collaborator:
Agency:
Barts & The London NHS Trust
Agency class:
Other
Collaborator:
Agency:
University College London Hospitals
Agency class:
Other
Source:
University College, London
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05880160
