Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction

NCT04680442 | Recruiting Phase 2

• 1 other identifier: PHRI.SCHOLAR-2
• Study Type: interventional
• Target: 130
• Locations: 3 countries
• Sites: 8

Brief Summary

Trastuzumab is an important treatment for HER 2 positive breast cancer. But trastuzumab can cause injury to the heart, and this is one of the main reasons it cannot be administered as planned. Heart injury can often be successfully treated using cardiac medications. The objectives of SCHOLAR-2 are to evaluate whether is it safe and effective to continue trastuzumab, pertuzumab or trastuzumab-emtansine (T-DM1) in patients with early stage HER-2 positive breast cancer despite mild, minimally symptomatic or asymptomatic systolic left ventricular dysfunction as compared with a guideline-driven approach of withholding or discontinuing trastuzumab, pertuzumab or trastuzumab-emtansine (T-DM1). In SCHOLAR-2, we will compare two thresholds of withholding or discontinuing trastuzumab/pertuzumab/trastuzumab-emtansine: a threshold that is currently advocated for by existing treatment practice guidelines versus a more aggressive threshold that allows trastuzumab/pertuzumab/trastuzumab-emtansine to continue at lower levels of LVEF than currently supported by guideline documents.

Conditions

Breast Cancer; Heart Failure

Outcome Measures

Primary Outcomes (2)

• primary efficacy outcome

  the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation

  one year

• co-primary safety outcomes

  1. LVEF at the close-out visit, and 2. The composite of NYHA class III or IV heart failure or cardiovascular death.

  one year

Secondary Outcomes (1)

• secondary outcome measures the composite of NYHA class III or IV heart failure, breast cancer relapse, or all-cause mortality.

  one year

Study Arms (2)

Control Group

ACTIVE COMPARATOR

Recommendations for continuing or holding trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) for the control group are guided by an adaptation of the 2008 Canadian recommendations.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Trastuzumab emtansine

Intervention Group

EXPERIMENTAL

The intervention group will continue to receive trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) in the setting of asymptomatic decline in LVEF up to an LVEF of 40% as outlined in the criteria listed in Table 3. For reasons of practicality, in the intervention group, the first dose of trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) after randomization can be administered up to 3 weeks late. This will allow time for the participant to be reviewed by a cardiologist and to receive ACE-I/angiotensin receptor blocker and/or beta-blocker, and for dose titration.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Trastuzumab emtansine

Interventions

Trastuzumab DRUG

Trastuzumab is a HER-2 targeting monoclonal antibody that improves overall survival and reduces the risk of recurrent disease in early stage HER-2 positive breast cancer.

Also known as: Herceptin, Herzuma, Ogivri, Trazimera, Kanjinti

Control Group; Intervention Group

Pertuzumab DRUG

Pertuzumab (also called 2C4, trade name Perjeta) is a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer; it also used in the same combination as a neoadjuvant in early HER2-positive breast cancer

Also known as: Perjeta

Control Group; Intervention Group

Trastuzumab emtansine DRUG

Ado-trastuzumab emtansine is approved to treat: Breast cancer that is HER2 positive and has already been treated with a taxane and trastuzumab.

Also known as: Kadcyla,

Control Group; Intervention Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage I-III HER-2 positive breast cancer
• Receiving adjuvant or neoadjuvant therapy with trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1)
• 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

You may not qualify if:

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

Sponsors & Collaborators

• Population Health Research Institute: lead

Study Sites (8)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035903 / 90410000, Brazil

RECRUITING

Irmandade Da Santa Casa De Misericórdia De Porto Alegre

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

RECRUITING

Hospital Alemão Oswaldo Cruz

São Paulo, São Paulo, 01327-903, Brazil

RECRUITING

Clínica de Pesquisa e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda

São Paulo, São Paulo, 1317000, 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, M5G 2N2, Canada

RECRUITING

E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation

Novosibirsk, 630055, Russia

SUSPENDED

MeSH Terms

Conditions

Breast Neoplasms; Heart Failure

Interventions

Trastuzumab; Ogivri; pertuzumab; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Darryl Leong, PhD. MBBSm

  McMaster University

  PRINCIPAL INVESTIGATOR

• Som Mukherjee, MD MSc FRCPC

  Hamilton Health Sciences Corporation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maha Mushtaha, BSc

CONTACT

9052973479; maha.mushtaha@phri.ca

Sumathy Rangarajan, MSc

CONTACT

9052973479; sumathy.rangarajan@phri.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 23, 2020
• Study Start: July 1, 2021
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (4); RU (1); CA (3)