A Phase I Clinical Study to Examine the Safety of Continued Treatment With Trastuzumab for Individuals With Overt Left Ventricular Dysfunction
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Safety outcomes
Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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
Intervention: standard-of-care treatments for LV impairment (Drug)
Outcomes
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.
Secondary Outcomes
No secondary outcomes reported