Heart FailurePhase 1SCHOLARNCT02907021
Safety of Continuing CHemotherapy in Overt Left Ventricular Dysfunction Using Antibodies to HER-2
A Phase 1 study testing standard-of-care treatments for LV impairment in people with Heart Failure and Breast Cancer, run by Population Health Research Institute at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Heart Failure, Breast Cancer
- What is being tested?
- standard-of-care treatments for LV impairment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 1 Nov 2016to 12 Apr 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Clinical Study to Examine the Safety of Continued Treatment With Trastuzumab for Individuals With Overt Left Ventricular Dysfunction
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.
Read the 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
- Being tested
- standard-of-care treatments for LV impairment
- Medical subject headings
- Heart Failure, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
standard-of-care treatments for LV impairmentDrug
Also called ACE-I and beta-blockers
Treat patients with mild or moderate LV impairment by standard-of-care treatments for LV impairment using ACE-I and beta-blockers
| Study group | Role | What they receive |
|---|---|---|
| Heart failure | Experimental | 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 Receives: Drug: standard-of-care treatments for LV impairment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%
Measured: one year
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.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2016 (estimated)
- Study start1 Nov 2016
- Primary completion12 Apr 2018
- Study completion12 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Population Health Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Darryl Leong, PhD. MBBSm, Principal investigator, Population Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02907021
- Sponsor's protocol ID
- SCHOLAR-2016
- Acronym
- SCHOLAR
- Status last verified
- Oct 2020
- First submitted
- 15 Sep 2016
- Last updated
- 9 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 34396157
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Study to Examine the Safety of Continued Treatment With Trastuzumab for Individuals With Overt Left Ventricular Dysfunction
- ClinicalTrials.gov ID
- NCT02907021
- Acronym / sponsor ID
- SCHOLAR / SCHOLAR-2016
- Conditions
- Heart Failure, Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Population Health Research InstituteUniversity, hospital or other
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 12 Apr 2018 (actual)
- Study completion
- 12 Apr 2018 (actual)
- First posted
- 20 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Heart failure | Experimental | Drug: standard-of-care treatments for LV impairmentTreat 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Stage I-III HER-2 positive breast cancer
- Receiving adjuvant therapy with trastuzumab
- Provide informed consent
- Exhibit LV dysfunction as evidenced by either
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| standard-of-care treatments for LV impairmentAlso: ACE-I and beta-blockersTreat patients with mild or moderate LV impairment by standard-of-care treatments for LV impairment using ACE-I and beta-blockers | Drug | Heart failure |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2020.
- Derived from this study: PubMed 34396157Leong 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darryl Leong, PhD. MBBSm principal investigator
Population Health Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing standard-of-care treatments for LV impairment in people with Heart Failure and Breast Cancer, run by Population Health Research Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety outcomes (time frame: one year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02907021, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2020.