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NCT Number: NCT04680442

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

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Cardiovascular Diseases Heart Diseases Heart Failure Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil

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About this study

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)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Trastuzumab

Drug

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

Pertuzumab

Drug

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

Trastuzumab Emtansine

Drug

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,

Primary outcomes

  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

    • LVEF at the close-out visit, and
    • The composite of NYHA class III or IV heart failure or cardiovascular death.

Secondary outcomes

  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.

Study contacts

Contact information is provided by the study sponsor or research team.

Maha Mushtaha, BSc

CONTACT

[email protected]

9052973479 ext. 41084

Sumathy Rangarajan, MSc

CONTACT

[email protected]

9052973479 ext. 40464

Sponsors and collaborators

Lead sponsor

Population Health Research Institute

Other

Registry information

Official study title

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

Acronym: SCHOLAR-2

Important dates

Study start
2021
Primary completion
2025
Study completion
2026
First posted
Dec 23, 2020
Registry last updated
Apr 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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