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

NCT ID: NCT04680442

Last Updated: 2025-04-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

130 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-01

Study Completion Date

2026-06-30

Brief Summary

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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.

Detailed Description

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SCHOLAR-2 is a Phase II open-label randomized controlled trial with blinded outcome event ascertainment with a target sample size of 130.

Control Group 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.

Intervention Group 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.

Study assessments will occur:

1. 3 weeks after randomization
2. 6 weeks after randomization
3. Follow-up at every 3 months thereafter until 12 months after the last dose of trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1)

Conditions

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Breast Cancer Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Control Group

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.

Group Type ACTIVE_COMPARATOR

Trastuzumab

Intervention Type 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.

Pertuzumab

Intervention Type 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

Trastuzumab emtansine

Intervention Type DRUG

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

Intervention Group

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.

Group Type EXPERIMENTAL

Trastuzumab

Intervention Type 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.

Pertuzumab

Intervention Type 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

Trastuzumab emtansine

Intervention Type DRUG

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

Interventions

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Trastuzumab

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.

Intervention Type DRUG

Pertuzumab

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

Intervention Type DRUG

Trastuzumab emtansine

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

Intervention Type DRUG

Other Intervention Names

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Herceptin, Herzuma, Ogivri, Trazimera, Kanjinti Perjeta Kadcyla,

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Population Health Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Darryl Leong, PhD. MBBSm

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Som Mukherjee, MD MSc FRCPC

Role: PRINCIPAL_INVESTIGATOR

Hamilton Health Sciences Corporation

Locations

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Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status RECRUITING

Irmandade Da Santa Casa De Misericórdia De Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status RECRUITING

Hospital Alemão Oswaldo Cruz

São Paulo, São Paulo, Brazil

Site Status RECRUITING

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

São Paulo, São Paulo, Brazil

Site Status RECRUITING

Juravnski Cancer Centre

Hamitlon, Ontario, Canada

Site Status RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Site Status RECRUITING

Toronto General Hospital, University Health Network

Toronto, Ontario, Canada

Site Status RECRUITING

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

Novosibirsk, , Russia

Site Status SUSPENDED

Countries

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Brazil Canada Russia

Central Contacts

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Maha Mushtaha, BSc

Role: CONTACT

9052973479 ext. 41084

Sumathy Rangarajan, MSc

Role: CONTACT

9052973479 ext. 40464

Facility Contacts

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Nathalia Santos

Role: primary

Rafael Zimmer

Role: backup

Nathalia Santos

Role: primary

Nathalia Santos

Role: primary

Nathalia Santos

Role: primary

Som Mukherjee

Role: primary

905-387-9711 ext. 63123

Kelsey Ross

Role: primary

Tiffanie Kei

Role: primary

Other Identifiers

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PHRI.SCHOLAR-2

Identifier Type: -

Identifier Source: org_study_id

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