Clinical trial NCT02907021: Safety of Continuing CHemotherapy in Overt Left Ventricular Dysfunction Using Antibodies to HER-2
Official title: A Phase I Clinical Study to Examine the Safety of Continued Treatment With Trastuzumab for Individuals With Overt Left Ventricular Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Breast Cancer
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2016-09-20
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Safety outcomes
timeFrame: one year
measure: Efficacy outcomes
timeFrame: one year
Secondary outcomes:
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
Study officials:
affiliation: Population Health Research Institute
name: Darryl Leong, PhD. MBBSm
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.