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

Официальное название

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

Обзор

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.

Подробное описание

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)

Вмешательства

• Препарат 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.
• Препарат 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
• Препарат 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.

Первичные конечные точки

• primary efficacy outcome [Срок оценки: one year]
• co-primary safety outcomes [Срок оценки: one year]

Вторичные конечные точки (1)

• secondary outcome measures the composite of NYHA class III or IV heart failure, breast cancer relapse, or all-cause mortality. [Срок оценки: one year]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Бразилия · 4 центра

• Hospital de Clínicas de Porto Alegre — Porto Alegre
• Irmandade Da Santa Casa De Misericórdia De Porto Alegre — Porto Alegre
• Hospital Alemão Oswaldo Cruz — São Paulo
• Clínica de Pesquisa e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda — São Paulo

Канада · 3 центра

• Juravnski Cancer Centre — Hamitlon
• Ottawa Hospital Research Institute — Ottawa
• Toronto General Hospital, University Health Network — Toronto

Россия · 1 центр

• E.Meshalkin National medical research center of the Ministry of Health of the Russian Fede — Novosibirsk

Идентификаторы

NCT: NCT04680442 · PHRI.SCHOLAR-2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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