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

October 7, 2020 updated by: Population Health Research Institute

A Phase I Clinical Study to Examine the Safety of Continued Treatment With Trastuzumab for Individuals With 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 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8V 1C3
        • Juravinski Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Heart failure
Treat the HER-2 positive breast cancer patients experiencing mild or moderate LV impairment by standard-of-care treatments for LV impairment using ACE-I and beta-blockers
Drug: standard-of-care treatments for LV impairment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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%
one year
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.
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Population Health Research Institute

Investigators

  • Principal Investigator: Darryl Leong, PhD. MBBSm, Population Health Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2016

Primary Completion (Actual)

April 12, 2018

Study Completion (Actual)

April 12, 2018

Study Registration Dates

First Submitted

September 15, 2016

First Submitted That Met QC Criteria

September 19, 2016

First Posted (Estimate)

September 20, 2016

Study Record Updates

Last Update Posted (Actual)

October 9, 2020

Last Update Submitted That Met QC Criteria

October 7, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCHOLAR-2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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