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

NCT ID: NCT02907021

Last Updated: 2020-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-01
• Study Completion Date: 2018-04-12

Brief 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.

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

Conditions

Heart Failure; Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

standard-of-care treatments for LV impairment

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

ACE-I and beta-blockers

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Population Health Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darryl Leong, PhD. MBBSm

Role: PRINCIPAL_INVESTIGATOR

Population Health Research Institute

Locations

Juravinski Hospital

Hamilton, Ontario, Canada

Countries

Canada

References

Leong DP, Cosman T, Alhussein MM, Kumar Tyagi N, Karampatos S, Barron CC, Wright D, Tandon V, Magloire P, Joseph P, Conen D, Devereaux PJ, Ellis PM, Mukherjee SD, Dhesy-Thind S. Safety of Continuing Trastuzumab Despite Mild Cardiotoxicity: A Phase I Trial. JACC CardioOncol. 2019 Jul 17;1(1):1-10. doi: 10.1016/j.jaccao.2019.06.004. eCollection 2019 Sep.

Reference Type: DERIVED

PMID: 34396157 (View on PubMed)

Other Identifiers

SCHOLAR-2016

Identifier Type: -

Identifier Source: org_study_id