NCT05880160

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
90

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Jul 2023

Typical duration for not_applicable

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 8, 2023

Completed
4 months until next milestone

First Posted

Study publicly available on registry

May 30, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

July 14, 2023

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2025

Completed
Last Updated

December 4, 2023

Status Verified

November 1, 2023

Enrollment Period

2.1 years

First QC Date

February 8, 2023

Last Update Submit

November 28, 2023

Conditions

CardiotoxicityHER2-positive Breast CancerHeart FailureCancer, Therapy-Related

Keywords

CardiotoxicityHER2-positive Breast CancerHeart FailureCancer, Therapy-Related

Outcome Measures

Primary Outcomes (1)

  • Relapse in Cardiotoxicity

    Number of participants with relapse in cardiotoxicity, defined based on International Cardio-Oncology Society 2021 Guidelines as (at least one of): 1. Asymptomatic left ventricular ejection fraction (LVEF) reduction by ≥10 percentage points to a LVEF of \<50% 2. Asymptomatic LVEF reduction by ≥5 percentage points to an LVEF of \<50% plus new relative decline in global longitudinal strain (GLS) by \>15% from baseline AND/OR new rise in cardiac biomarkers (\>2 fold increase in N-terminal pro B-type natriuretic peptide \[NTproBNP\] to \>400ng/L, or high sensitivity Troponin \>99th percentile) 3. Clinical heart failure (based on symptoms and clinical examination) with at least one of the following: fall in LVEF ≥5%, increase in cardiac biomarkers (as above), relative fall in GLS \> 15%, new arrhythmia (excluding ectopy)

    12 months

Secondary Outcomes (11)

  • Cardiac Biomarkers (N-terminal pro B-type natriuretic peptide [NT-proBNP])

    12 months

  • Cardiac Biomarkers (Troponin T)

    12 months

  • Quality of life (Kansas City Cardiomyopathy Questionnaire)

    12 months

  • Quality of life (Minnesota Living with Heart Failure Questionnaire)

    12 months

  • Heart rate

    12 months

  • +6 more secondary outcomes

Study Arms (2)

Treatment Withdrawal

EXPERIMENTAL

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). Medications will be down titrated in a phased process every 2 weeks over 16 weeks maximum. Drug doses will be reduced by 50% every 2 weeks, until the patient is taking 25% or less of the maximum recommended dose at which point they will be stopped. Monitoring with fortnightly virtual consultations will confirm 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 cardiovascular magnetic resonance scans and symptom and disutility questionnaires will be undertaken.

Other: Phased withdrawal of heart failure medications

Treatment Continuation

NO INTERVENTION

Participants will continue their current heart failure/ cardioprotective treatments. 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 cardiovascular magnetic resonance scans and symptom and disutility questionnaires will be undertaken.

Interventions

Phased withdrawal of heart failure medicationsOTHER

As per arm/group description

Treatment Withdrawal

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult participants (\>18 years)
  • 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).
  • 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.

You may not qualify if:

  • Advanced/ metastatic HER2 positive breast cancer requiring ongoing HER2 therapies or with life expectancy \<12months.
  • Patients classed as high/very high cardiovascular risk according to the International Cardio-Oncology Society (ICOS) risk stratification
  • Patients with LVEF \<50% prior to HER2-therapy initiation or on completion of anthracycline treatment
  • Patients with ongoing indications for the cardioprotective medication - ACE inhibitors, ARBs and/or beta-blockers
  • Patients with absolute contraindications to cardiovascular magnetic resonance scans (CMR).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

St Bartholemew's Hospital

London, EC1A 7BE, United Kingdom

RECRUITING

University College London Hospital

London, NW1 2BU, United Kingdom

RECRUITING

Related Publications (1)

  • Dowsing B, Dehbi HM, Chung R, Pedra J, Worn O, Artico J, Schmid P, Roylance R, Kellman P, Moon JC, Crake T, Westwood M, Ghosh A, Andres MS, Nazir MS, Lyon AR, Chen D, Walker M, Manisty CH. HER-SAFE study design: an open-label, randomised controlled trial to investigate the safety of withdrawal of pharmacological treatment for recovered HER2-targeted therapy-related cardiac dysfunction. BMJ Open. 2025 Feb 5;15(2):e091917. doi: 10.1136/bmjopen-2024-091917.

    PMID: 39909533DERIVED

MeSH Terms

Conditions

CardiotoxicityHeart FailureNeoplasms, Second Primary

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersRadiation InjuriesWounds and InjuriesNeoplasms

Study Officials

  • Charlotte Manisty

    UCL

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Dowsing, MBBS MSc BSc

CONTACT

+447912148972benjamin.dowsing@nhs.net

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Masking Details
Open label
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 8, 2023

First Posted

May 30, 2023

Study Start

July 14, 2023

Primary Completion

September 1, 2025

Study Completion

September 1, 2025

Last Updated

December 4, 2023

Record last verified: 2023-11

Data Sharing

IPD Sharing
Will not share

Locations

GB(2)