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

Primary Purpose

Breast Cancer, Heart Failure

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Trastuzumab
Pertuzumab
Trastuzumab emtansine
Sponsored by
Population Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital de Clínicas de Porto AlegreRecruiting
  • Irmandade Da Santa Casa De Misericórdia De Porto AlegreRecruiting
  • Hospital Alemão Oswaldo CruzRecruiting
  • Clínica de Pesquisa e Centro de Estudos em Oncologia Ginecológica e Mamária LtdaRecruiting
  • Juravnski Cancer CentreRecruiting
  • Ottawa Hospital Research InstituteRecruiting
  • Toronto General Hospital, University Health NetworkRecruiting
  • E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control Group

Intervention Group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

primary efficacy outcome
the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation
co-primary safety outcomes
LVEF at the close-out visit, and The composite of NYHA class III or IV heart failure or cardiovascular death.

Secondary Outcome Measures

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

Full Information

First Posted
December 17, 2020
Last Updated
March 24, 2023
Sponsor
Population Health Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04680442
Brief Title
Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction
Acronym
SCHOLAR-2
Official Title
Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction: A Randomized, Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2021 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Population Health Research Institute

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control Group
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Intervention Group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin, Herzuma, Ogivri, Trazimera, Kanjinti
Intervention Description
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
Intervention Name(s)
Pertuzumab
Other Intervention Name(s)
Perjeta
Intervention Description
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
Intervention Name(s)
Trastuzumab emtansine
Other Intervention Name(s)
Kadcyla,
Intervention Description
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 Information:
Title
primary efficacy outcome
Description
the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation
Time Frame
one year
Title
co-primary safety outcomes
Description
LVEF at the close-out visit, and The composite of NYHA class III or IV heart failure or cardiovascular death.
Time Frame
one year
Secondary Outcome Measure Information:
Title
secondary outcome measures the composite of NYHA class III or IV heart failure, breast cancer relapse, or all-cause mortality.
Description
the composite of NYHA class III or IV heart failure, breast cancer relapse, or all-cause mortality.
Time Frame
one year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maha Mushtaha, BSc
Phone
9052973479
Ext
41084
Email
maha.mushtaha@phri.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Sumathy Rangarajan, MSc
Phone
9052973479
Ext
40464
Email
sumathy.rangarajan@phri.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Darryl Leong, PhD. MBBSm
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Som Mukherjee, MD MSc FRCPC
Organizational Affiliation
Hamilton Health Sciences Corporation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035903 / 90410000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalia Santos
Email
natsantos@haoc.com.br
First Name & Middle Initial & Last Name & Degree
Rafael Zimmer
Email
rzimmer@hcpa.edu.br
First Name & Middle Initial & Last Name & Degree
Felipe Homem Valle
Facility Name
Irmandade Da Santa Casa De Misericórdia De Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90050-170
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalia Santos
Email
natsantos@haoc.com
First Name & Middle Initial & Last Name & Degree
Katsuki Tiscoski
Facility Name
Hospital Alemão Oswaldo Cruz
City
São Paulo
ZIP/Postal Code
01327-903
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalia Santos
Email
natsantos@haoc.com.br
First Name & Middle Initial & Last Name & Degree
Pedro Exman
Facility Name
Clínica de Pesquisa e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda
City
São Paulo
ZIP/Postal Code
1317000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalia Santos
Email
natsantos@haoc.com.br
First Name & Middle Initial & Last Name & Degree
André Mattar
Facility Name
Juravnski Cancer Centre
City
Hamitlon
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Som Mukherjee
Phone
905-387-9711
Ext
63123
Email
mukherjee@HHSC.CA
First Name & Middle Initial & Last Name & Degree
Som Mukherjee
Facility Name
Ottawa Hospital Research Institute
City
Ottawa
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelsey Ross
Email
kelross@ohri.ca
First Name & Middle Initial & Last Name & Degree
Marie-France Savard
Facility Name
Toronto General Hospital, University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tiffanie Kei
Email
tiffanie.kei@uhn.ca
First Name & Middle Initial & Last Name & Degree
Dinesh Thavendiranathan
Facility Name
E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation
City
Novosibirsk
ZIP/Postal Code
630055
Country
Russian Federation
Individual Site Status
Suspended

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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