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

March 13, 2024 updated by: Population Health Research Institute

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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)

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • São Paulo, Brazil, 01327-903
        • Recruiting
        • Hospital Alemão Oswaldo Cruz
        • Contact:
        • Principal Investigator:
          • Pedro Exman
      • São Paulo, Brazil, 1317000
        • Recruiting
        • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
        • Contact:
        • Principal Investigator:
          • Andre Mattar
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170
        • Recruiting
        • Irmandade da Santa Casa de Misericordia de Porto Alegre
        • Contact:
        • Principal Investigator:
          • Katsuki Tiscoski
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90035903 / 90410000
  • Canada
    • Ontario
      • Hamitlon, Ontario, Canada
        • Recruiting
        • Juravnski Cancer Centre
        • Contact:
        • Principal Investigator:
          • Som Mukherjee
      • Ottawa, Ontario, Canada
        • Recruiting
        • Ottawa Hospital Research Institute
        • Contact:
        • Principal Investigator:
          • Marie-France Savard
      • Toronto, Ontario, Canada, M5G 2N2
        • Recruiting
        • Toronto General Hospital, University Health Network
        • Contact:
        • Principal Investigator:
          • Dinesh Thavendiranathan
  • Russian Federation
      • Novosibirsk, Russian Federation, 630055
        • Suspended
        • E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: 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.
Other Names:
  • Herceptin, Herzuma, Ogivri, Trazimera, Kanjinti
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
Other Names:
  • Perjeta
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.
Other Names:
  • Kadcyla,
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.
Drug: 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.
Other Names:
  • Herceptin, Herzuma, Ogivri, Trazimera, Kanjinti
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
Other Names:
  • Perjeta
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.
Other Names:
  • Kadcyla,

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
primary efficacy outcome
Time Frame: one year
the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation
one year
co-primary safety outcomes
Time Frame: one year
  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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
secondary outcome measures the composite of NYHA class III or IV heart failure, breast cancer relapse, or all-cause mortality.
Time Frame: one year
the composite of NYHA class III or IV heart failure, breast cancer relapse, or all-cause mortality.
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Population Health Research Institute

Investigators

  • Principal Investigator: Darryl Leong, PhD. MBBSm, McMaster University
  • Principal Investigator: Som Mukherjee, MD MSc FRCPC, Hamilton Health Sciences Corporation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2021

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

December 17, 2020

First Submitted That Met QC Criteria

December 17, 2020

First Posted (Actual)

December 23, 2020

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PHRI.SCHOLAR-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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