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

Breast Cancer Clinical Trial

— SCHOLAR-2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04680442
• Other study ID #: PHRI.SCHOLAR-2
• Status: Recruiting
• Phase: Phase 2
• Start date: July 1, 2021
• Est. completion date: June 1, 2025

Study information

• Verified date: March 2024
• Source: Population Health Research Institute
• Contact: Maha Mushtaha, BSc
• Phone: 9052973479
• Email: maha.mushtaha[@]phri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: June 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Heart Failure
• Ventricular Dysfunction
• Ventricular Dysfunction, Left

Intervention

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.
• 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.

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade Da Santa Casa De Misericórdia De Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Clínica de Pesquisa e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda	São Paulo
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo
Canada	Juravnski Cancer Centre	Hamitlon	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Toronto General Hospital, University Health Network	Toronto	Ontario
Russian Federation	E.Meshalkin National medical research center of the Ministry of Health of the Russian Federation	Novosibirsk

Sponsors (1)

Lead Sponsor	Collaborator
Population Health Research Institute

Countries where clinical trial is conducted

Brazil,  Canada,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	primary efficacy outcome	the proportion of participants completing trastuzumab, pertuzumab, or trastuzumab-emtansine (T-DM1) as planned at its initiation	one year
Primary	co-primary safety outcomes	LVEF at the close-out visit, and; The composite of NYHA class III or IV heart failure or cardiovascular death.	one year
Secondary	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.	one year