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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02907021
Recruitment Status : Recruiting
First Posted : September 20, 2016
Last Update Posted : April 6, 2018
Information provided by (Responsible Party):
Population Health Research Institute

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.

Condition or disease Intervention/treatment Phase
Heart Failure Breast Cancer Drug: standard-of-care treatments for LV impairment Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Study to Examine the Safety of Continued Treatment With Trastuzumab for Individuals With Overt Left Ventricular Dysfunction
Actual Study Start Date : November 1, 2016
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

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 Name: ACE-I and beta-blockers

Primary Outcome Measures :
  1. 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%

  2. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02907021

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Contact: Yongning Ou, M.Sc. 1-905-527-4322 ext 40496

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Canada, Ontario
Juravinski Hospital Recruiting
Hamilton, Ontario, Canada, L8V 1C3
Contact: Tammy Cosmin, RN(EC), PhD         
Sponsors and Collaborators
Population Health Research Institute
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Principal Investigator: Darryl Leong, PhD. MBBSm Population Health Research Institute

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Responsible Party: Population Health Research Institute Identifier: NCT02907021     History of Changes
Other Study ID Numbers: SCHOLAR-2016
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: April 6, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
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Heart Failure
Ventricular Dysfunction
Ventricular Dysfunction, Left
Heart Diseases
Cardiovascular Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs