Recruiting
Phase 2

HER-2 Directed Therapy

Sponsor:

Population Health Research Institute

Code:

NCT04680442

Conditions

Breast Cancer

Heart Failure

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

Trastuzumab

Pertuzumab

Trastuzumab emtansine

Study Details

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

Study ID

NCT04680442

Start date

Jul 1, 2021

Status verified date

Apr, 2025

Completion date

Jun 30, 2026

Anticipated

Primary completion date

Dec 31, 2025

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

130 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: 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.

experimental: 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.

Interventions

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.

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

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.

Primary outcome measure

  • primary efficacy outcome [ Time Frame: one year ]
  • co-primary safety outcomes [ Time Frame: one year ]

Central Contacts and Locations

Central contacts

Maha Mushtaha, BSc

9052973479maha.mushtaha@phri.ca

Sumathy Rangarajan, MSc

9052973479sumathy.rangarajan@phri.ca

Locations

Juravnski Cancer Centre

Recruiting

Hamitlon, Ontario, Canada

Contacts

Som Mukherjee

905-387-9711mukherjee@HHSC.CA

Principal Investigator:

Som Mukherjee

Ottawa Hospital Research Institute

Recruiting

Ottawa, Ontario, Canada

Contacts

Kelsey Ross

kelross@ohri.ca

Principal Investigator:

Marie-France Savard

Toronto General Hospital, University Health Network

Recruiting

Toronto, Ontario, Canada, M5G 2N2

Contacts

Tiffanie Kei

tiffanie.kei@uhn.ca

Principal Investigator:

Dinesh Thavendiranathan

More Information

Sponsor

Population Health Research Institute

Last update posted

Apr 6, 2025

Last verified

Apr, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Population Health Research Institute on 2025-04-06.