Safety of Continuing CHemotherapy in Overt Left Ventricular Dysfunction Using Antibodies to HER-2

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 aim of SCHOLAR is to evaluate whether it is safe to continue trastuzumab in individuals with mild or moderate cardiac injury, while treating them with appropriate cardiac medications. In this way the investigators hope to be able to optimise the delivery of a treatment to patients with breast cancer that has proven survival benefits, especially when administered for a full 12-month course.

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Key information

Conditions

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

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Juravinski Hospital

Hamilton, Ontario, L8V 1C3, Canada

About this study

The SCHOLAR study design will be a modified phase I, non-randomized clinical study.

Initially a cohort of 5 participants will be enrolled. They will continue to receive trastuzumab. All participants in SCHOLAR will also be prescribed standard-of-care treatment for patients with LV systolic dysfunction, including the beta-blocker, carvedilol, and the ACE-I, ramipril, as tolerated, at the maximum doses tolerated, up to carvedilol 25mg BID and ramipril 10mg once daily. If at any time 1 or more of the first 5 participants develop cDLT, de-escalation will occur. De-escalation will involve a change in the eligibility criteria to exclude patients with LVEF <45% and patients with NYHA class II, III, or IV heart failure. A further 5 patients will then be recruited. If 2 or more of the second 5 participants develop cDLT after de-escalation, the intervention will be considered unsafe, and the study will be closed. If the intervention is considered safe either using the initial eligibility criteria or the de-escalated eligibility criteria, the study will be closed after 20 participants have been recruited. If at any time during the study >20% of participants develop cDLT, the intervention will be considered unsafe, and the study will be closed.

Patients will be seen by a cardiologist at the following time points (referenced from the baseline visit): baseline, 3 weeks ± 1 week, 6 weeks ± 1 week, 3 months ± 1 week, 6 months ± 1 week, 9 months ± 1 week, 12 month ± 1 week

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 therapy with trastuzumab
Provide informed consent
Exhibit LV dysfunction as evidenced by either

LVEF between 40% and the lower limit for normal (i.e. <54% in women or < 52% in men18), or
LVEF within normal limits (i.e. ≥54% in women or ≥52% in men) and NYHA class II heart failure symptoms within the past year, or
A fall in LVEF of ≥15% from baseline

Exclusion criteria

Patients will not be eligible for SCHOLAR if they have any of the following:

NYHA class III or IV heart failure
Systolic blood pressure <90mmHg
Current use of both ACE-I/angiotensin receptor blocker and beta-blocker
Contra-indication to both ACE-I/angiotensin receptor blocker and beta-blocker

Treatment and study plan

standard-of-care treatments for LV impairment

Drug

Treat patients with mild or moderate LV impairment by standard-of-care treatments for LV impairment using ACE-I and beta-blockers

Other names: ACE-I and beta-blockers

Primary outcomes

Safety outcomes

Time frame: one year

The primary safety outcome will be the development of cardiac dose-limiting toxicity (cDLT), defined as the occurrence of any of a)cardiovascular death, b)left ventricular ejection fraction (LVEF) <40% together with any heart failure symptoms, or c) LVEF <35%
Efficacy outcomes

Time frame: one year

The efficacy outcome will be the number of trastuzumab cycles completed after enrollment as a proportion of the originally planned number of trastuzumab cycles.

Sponsors and collaborators

Lead sponsor

Population Health Research Institute

Other

Registry information

Official study title

A Phase I Clinical Study to Examine the Safety of Continued Treatment With Trastuzumab for Individuals With Overt Left Ventricular Dysfunction

Acronym: SCHOLAR

Important dates

Study start: 2016
Primary completion: 2018
Study completion: 2018
First posted: Sep 20, 2016
Registry last updated: Oct 9, 2020

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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Completed