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

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ClinicalTrials.gov Identifier: NCT04680442
Recruitment Status : Recruiting
First Posted : December 23, 2020
Last Update Posted : June 27, 2022
Sponsor:
Information provided by (Responsible Party):
Population Health Research Institute

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Heart Failure Drug: Trastuzumab Drug: Pertuzumab Drug: Trastuzumab emtansine Phase 2

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction: A Randomized, Controlled Trial
Actual Study Start Date : July 1, 2021
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Kadcyla,




Primary Outcome Measures :
  1. primary efficacy outcome [ Time Frame: one year ]
    the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation

  2. 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.


Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04680442


Contacts
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Contact: Maha Mushtaha, BSc 9052973479 ext 41084 maha.mushtaha@phri.ca
Contact: Sumathy Rangarajan, MSc 9052973479 ext 40464 sumathy.rangarajan@phri.ca

Locations
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Canada, Ontario
Juravnski Cancer Centre Recruiting
Hamitlon, Ontario, Canada
Contact: Som Mukherjee    905-387-9711 ext 63123    mukherjee@HHSC.CA   
Principal Investigator: Som Mukherjee         
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada
Contact: Kelsey Ross       kelross@ohri.ca   
Principal Investigator: Marie-France Savard         
Toronto General Hospital, University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2N2
Contact: Tiffanie Kei       tiffanie.kei@uhn.ca   
Principal Investigator: Dinesh Thavendiranathan         
Russian Federation
E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation Recruiting
Novosibirsk, Russian Federation, 630055
Contact: Dmitry Sirota       d_sirota@meshalkin.ru   
Principal Investigator: Dmitry Sirota         
Sponsors and Collaborators
Population Health Research Institute
Investigators
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Principal Investigator: Darryl Leong, PhD. MBBSm McMaster University
Principal Investigator: Som Mukherjee, MD MSc FRCPC Hamilton Health Sciences Corporation
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Responsible Party: Population Health Research Institute
ClinicalTrials.gov Identifier: NCT04680442    
Other Study ID Numbers: PHRI.SCHOLAR-2
First Posted: December 23, 2020    Key Record Dates
Last Update Posted: June 27, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Ventricular Dysfunction
Ventricular Dysfunction, Left
Heart Diseases
Cardiovascular Diseases
Trastuzumab
Pertuzumab
Ado-Trastuzumab Emtansine
Maytansine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action