Ignite Creation Date:
2025-12-24 @ 12:45 PM
Ignite Modification Date:
2025-12-30 @ 9:33 AM
Study NCT ID:
NCT03418961
Status:
RECRUITING
Last Update Posted:
2025-10-08
First Post:
2018-01-02
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
S1501 Dual Observational and Randomized Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity
Sponsor:
SWOG Cancer Research Network
Organization:
Study Overview
Official Title:
Prospective Observational Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity
Status:
RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This trial has two cohorts of patients with human epidermal growth factor receptor (HER)-2-positive breast cancer that has spread to other places in the body. All patients must be receiving trastuzumab-based treatment. Both cohorts are being observed for cardiac toxicity. The largest cohort (currently open to accrual) is observational, and contains patients who are taking a beta blocker, ACE inhibitor, or ARB as well as their trastuzumab-based treatment. The goal is to understand how common cardiac problems are in this group of patients at high risk. The smaller cohort (currently closed to accrual) is randomized. Patients in this second cohort are randomized to either carvedilol or no treatment, with the goal of seeing whether carvedilol (used to treat heart failure and high blood pressure) may prevent the heart from side effects of chemotherapy.
Detailed Description:
PRIMARY OBJECTIVES:
I. To estimate the 2-year cumulative incidence of cardiac dysfunction and/or predefined cardiac events in patients with metastatic breast cancer receiving trastuzumab-based HER-2 targeted therapy and beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitor.
II. To develop a model including clinical factors and potential biomarkers to predict risk of cardiac dysfunction and/or predefined cardiac events in patients with metastatic breast cancer receiving trastuzumab-based HER-2 targeted therapy and beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitor.
SECONDARY OBJECTIVES:
I. To assess whether prophylactic beta blocker therapy with carvedilol compared with no prophylaxis reduces the risk of cardiac dysfunction and/or predefined cardiac events in patients with metastatic breast cancer receiving trastuzumab-based HER-2 targeted therapy.
II. To evaluate if prophylactic carvedilol compared with no prophylaxis results in a longer time to first interruption of trastuzumab-based HER-2 targeted therapy due to either cardiac dysfunction or events.
III. To compare the local and central reads of left ventricular ejection fraction (LVEF) and strain and assess if strain changes can predict drop in ejection fraction.
IV. Assess if strain can be used in the community as a marker of cardiotoxicity.
TERTIARY OBJECTIVES:
I. To evaluate the lle655Val and Alall70Pro single nucleotide polymorphisms (SNPs) of the HER-2 gene as a predictive biomarker of study-defined cardiac dysfunction and/or predefined cardiac events.
II. To evaluate plasma neuregulin-1 at baseline and over study time as a predictive biomarker of study-defined cardiac dysfunction and/or predefined cardiac events.
III. To evaluate the feasibility of local labs performing serial left ventricular strain in an NCTN group setting, with the goal of 75% of patients contributing both a baseline and at least one follow-up strain measurement.
IV. To bank blood for future translational medicine studies such as brain natriuretic peptide (BNP), additional SNPs, and high sensitivity troponin.
OUTLINE: Patients are randomized to 1 of 2 arms. Patients taking beta blocker, ARB, or ACE inhibitor at registration are assigned to Arm III.
ARM I: Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive carvedilol orally (PO) twice daily (BID). Courses repeat every 12 weeks for 108 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive no study intervention for up to 108 weeks.
ARM III: Patients undergo observation for up to 108 weeks.
I. To estimate the 2-year cumulative incidence of cardiac dysfunction and/or predefined cardiac events in patients with metastatic breast cancer receiving trastuzumab-based HER-2 targeted therapy and beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitor.
II. To develop a model including clinical factors and potential biomarkers to predict risk of cardiac dysfunction and/or predefined cardiac events in patients with metastatic breast cancer receiving trastuzumab-based HER-2 targeted therapy and beta blockers, angiotensin receptor blocker (ARB), or angiotensin converting enzyme (ACE) inhibitor.
SECONDARY OBJECTIVES:
I. To assess whether prophylactic beta blocker therapy with carvedilol compared with no prophylaxis reduces the risk of cardiac dysfunction and/or predefined cardiac events in patients with metastatic breast cancer receiving trastuzumab-based HER-2 targeted therapy.
II. To evaluate if prophylactic carvedilol compared with no prophylaxis results in a longer time to first interruption of trastuzumab-based HER-2 targeted therapy due to either cardiac dysfunction or events.
III. To compare the local and central reads of left ventricular ejection fraction (LVEF) and strain and assess if strain changes can predict drop in ejection fraction.
IV. Assess if strain can be used in the community as a marker of cardiotoxicity.
TERTIARY OBJECTIVES:
I. To evaluate the lle655Val and Alall70Pro single nucleotide polymorphisms (SNPs) of the HER-2 gene as a predictive biomarker of study-defined cardiac dysfunction and/or predefined cardiac events.
II. To evaluate plasma neuregulin-1 at baseline and over study time as a predictive biomarker of study-defined cardiac dysfunction and/or predefined cardiac events.
III. To evaluate the feasibility of local labs performing serial left ventricular strain in an NCTN group setting, with the goal of 75% of patients contributing both a baseline and at least one follow-up strain measurement.
IV. To bank blood for future translational medicine studies such as brain natriuretic peptide (BNP), additional SNPs, and high sensitivity troponin.
OUTLINE: Patients are randomized to 1 of 2 arms. Patients taking beta blocker, ARB, or ACE inhibitor at registration are assigned to Arm III.
ARM I: Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive carvedilol orally (PO) twice daily (BID). Courses repeat every 12 weeks for 108 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive no study intervention for up to 108 weeks.
ARM III: Patients undergo observation for up to 108 weeks.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| UG1CA189974 | NIH | None | https://reporter.nih.gov/quic… | View |
| NCI-2016-01047 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| S1501 | OTHER | SWOG | View | |
| SWOG-S1501 | OTHER | DCP | View |