Continuing HER-2 therapy in patients with heart dysfunction

Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction: A Randomized, Controlled Trial

This study is testing if people with early-stage HER-2 positive breast cancer and mild heart issues can safely continue their HER-2 treatments while taking heart medications, instead of stopping their cancer treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Sex: All
• Sponsor: Population Health Research Institute (other)
• Drugs / interventions: trastuzumab, pertuzumab
• Locations: 8 sites (Porto Alegre, Rio Grande do Sul and 7 other locations)
• Trial ID: NCT04680442 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of continuing HER-2 directed therapies, such as trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1), in patients with early-stage HER-2 positive breast cancer who exhibit mild left ventricular dysfunction. Participants are randomly assigned to either continue their treatment despite heart dysfunction or follow standard guidelines that recommend discontinuation. The study aims to determine if a more aggressive treatment approach can be safely implemented while managing heart health with cardiac medications. Assessments will occur at various intervals to monitor patient outcomes over a year.

Who should consider this trial

Good fit: Ideal candidates are individuals with stage I-III HER-2 positive breast cancer who are undergoing treatment and have mild left ventricular dysfunction.

Not a fit: Patients with severe heart failure (NYHA class III or IV) or significant heart dysfunction (LVEF <40%) may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could allow patients to continue effective breast cancer treatment while managing heart health, potentially improving survival rates.

How similar studies have performed: Other studies have explored similar approaches, but this specific methodology is relatively novel in the context of HER-2 directed therapy and heart dysfunction.

Eligibility criteria

Inclusion Criteria:

1. Stage I-III HER-2 positive breast cancer
2. Receiving adjuvant or neoadjuvant therapy with trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1)
3. Evidence of left ventricular dysfunction, as defined by at least one of:

   a) LVEF \< 54% or b) LVEF ≥54% and either i) fall in LVEF of ≥15% from prior to trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) exposure, or ii) New York Heart Association (NYHA) class II heart failure symptoms within the past 6 months

Exclusion Criteria:

1. Current use of both angiotensin converting enzyme inhibitor (ACEI) /angiotensin receptor blocker (ARB) and beta-blocker
2. Contra-indication to both ACE-I/ARB and beta-blockers
3. NYHA class III or IV heart failure
4. LVEF \<40%
5. Systolic blood pressure \<100mmHg
6. Current or planned pregnancy or breastfeeding

Where this trial is running

Porto Alegre, Rio Grande do Sul and 7 other locations

• Hospital de Clínicas de Porto Alegre — Porto Alegre, Rio Grande do Sul, Brazil (RECRUITING)
• Irmandade Da Santa Casa De Misericórdia De Porto Alegre — Porto Alegre, Rio Grande do Sul, Brazil (RECRUITING)
• Hospital Alemão Oswaldo Cruz — São Paulo, São Paulo, Brazil (RECRUITING)
• Clínica de Pesquisa e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda — São Paulo, São Paulo, Brazil (RECRUITING)
• Juravnski Cancer Centre — Hamitlon, Ontario, Canada (RECRUITING)
• Ottawa Hospital Research Institute — Ottawa, Ontario, Canada (RECRUITING)
• Toronto General Hospital, University Health Network — Toronto, Ontario, Canada (RECRUITING)
• E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation — Novosibirsk, Russia (SUSPENDED)

Study contacts

• Principal investigator: Darryl Leong, PhD. MBBSm — McMaster University
• Study coordinator: Maha Mushtaha, BSc

Conditions: Breast Cancer, Heart Failure