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

Breast Cancer Clinical Trial

— SCHOLAR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02907021
• Other study ID #: SCHOLAR-2016
• Status: Completed
• Phase: Phase 1
• Start date: November 1, 2016
• Est. completion date: April 12, 2018

Study information

• Verified date: October 2020
• Source: Population Health Research Institute
• Contact: n/a
• 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 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 12, 2018
• Est. primary completion date: April 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Canada	Juravinski Hospital	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Population Health Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety outcomes	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
Primary	Efficacy outcomes	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