Breast CancerPhase 2SCHOLAR-2NCT04680442
Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction
A Phase 2 study testing Trastuzumab, Pertuzumab and Trastuzumab emtansine in people with Breast Cancer and Heart Failure, run by Population Health Research Institute at 8 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Breast Cancer, Heart Failure
- What is being tested?
- Trastuzumab, Pertuzumab and Trastuzumab emtansine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 1 Jul 2021to 30 Jun 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- 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
Who cannot join
- 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
Trial locations and contacts
8 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
8 sites in 3 countries
Brazil4 sites, 4 recruiting
- Recruiting
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035903 / 90410000
Nathalia Santos, natsantos@haoc.com.br
Rafael Zimmer, rzimmer@hcpa.edu.br
- Recruiting
Irmandade Da Santa Casa De Misericórdia De Porto Alegre
Porto Alegre, Rio Grande do Sul, 90050-170
Nathalia Santos, natsantos@haoc.com
Katsuki Tiscoski
- Recruiting
Hospital Alemão Oswaldo Cruz
São Paulo, São Paulo, 01327-903
Nathalia Santos, natsantos@haoc.com.br
Pedro Exman
- Recruiting
Clínica de Pesquisa e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda
São Paulo, São Paulo, 1317000
Nathalia Santos, natsantos@haoc.com.br
André Mattar
Canada3 sites, 3 recruiting
- Recruiting
Juravnski Cancer Centre
Hamitlon, Ontario
Som Mukherjee, 905-387-9711 ext. 63123, mukherjee@HHSC.CA
Som Mukherjee
- Recruiting
Ottawa Hospital Research Institute
Ottawa, Ontario
Kelsey Ross, kelross@ohri.ca
Marie-France Savard
- Recruiting
Toronto General Hospital, University Health Network
Toronto, Ontario, M5G 2N2
Tiffanie Kei, tiffanie.kei@uhn.ca
Dinesh Thavendiranathan
Russia1 site
- Suspended
E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation
Novosibirsk, 630055
About this study
Official title: 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.
Read the 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)
- Conditions
- Breast Cancer, Heart Failure
- Being tested
- Trastuzumab, Pertuzumab, Trastuzumab emtansine
- Medical subject headings
- Breast Neoplasms, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin, Herzuma, Ogivri, Trazimera, Kanjinti
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.
PertuzumabDrug
Also called Perjeta
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 emtansineDrug
Also called Kadcyla,
Ado-trastuzumab emtansine is approved to treat: Breast cancer that is HER2 positive and has already been treated with a taxane and trastuzumab.
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Active comparator | 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. Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Trastuzumab emtansine |
| Intervention Group | Experimental | 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. Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Trastuzumab emtansine |
What is being measured
The primary outcome is the main question the study is designed to answer.
primary efficacy outcome
the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation
Measured: one year
co-primary safety outcomes
- LVEF at the close-out visit, and
- The composite of NYHA class III or IV heart failure or cardiovascular death.
Measured: one year
Secondary outcomes (1)
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.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2020
- Study start1 Jul 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Darryl Leong, PhD. MBBSm, Principal investigator, McMaster UniversitySom Mukherjee, MD MSc FRCPC, Principal investigator, Hamilton Health Sciences Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04680442
- Sponsor's protocol ID
- PHRI.SCHOLAR-2
- Acronym
- SCHOLAR-2
- Status last verified
- Apr 2025
- First submitted
- 17 Dec 2020
- Last updated
- 6 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Continuing HER-2 Directed Therapy in Overt Left Ventricular Dysfunction: A Randomized, Controlled Trial
- ClinicalTrials.gov ID
- NCT04680442
- Acronym / sponsor ID
- SCHOLAR-2 / PHRI.SCHOLAR-2
- Conditions
- Breast Cancer, Heart Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Population Health Research InstituteUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 23 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | Active comparator | Drug: Trastuzumab, Drug: Pertuzumab, Drug: Trastuzumab emtansineRecommendations 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 | Experimental | Drug: Trastuzumab, Drug: Pertuzumab, Drug: Trastuzumab emtansineThe 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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:
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabAlso: Herceptin, Herzuma, Ogivri, Trazimera, KanjintiTrastuzumab 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. | Drug | Control Group, Intervention Group |
| PertuzumabAlso: PerjetaPertuzumab (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 | Drug | Control Group, Intervention Group |
| Trastuzumab emtansineAlso: Kadcyla,Ado-trastuzumab emtansine is approved to treat: Breast cancer that is HER2 positive and has already been treated with a taxane and trastuzumab. | Drug | Control Group, Intervention Group |
Primary outcome
primary efficacy outcome
Time frame: one year
the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation
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.
1 secondary outcome
secondary outcome measures the composite of NYHA class III or IV heart failure, breast cancer relapse, or all-cause mortality.
Time frame: one year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Darryl Leong, PhD. MBBSm principal investigator
McMaster University
Som Mukherjee, MD MSc FRCPC principal investigator
Hamilton Health Sciences Corporation
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab, Pertuzumab and Trastuzumab emtansine in people with Breast Cancer and Heart Failure, run by Population Health Research Institute at 8 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Brazil, Canada, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maha Mushtaha, BSc (9052973479 ext. 41084, maha.mushtaha@phri.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
primary efficacy outcome (time frame: one year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2025.