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RecruitingNCT03418961

S1501 Dual Observational and Randomized Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity

Prospective Observational Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity

Status
Recruiting
Phase
Phase 3
Study type
Interventional
Enrollment
491 (estimated)
Sponsor
SWOG Cancer Research Network · Network
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Conditions

Interventions

TypeNameDescription
DRUGCarvedilolGiven PO
OTHERLaboratory Biomarker AnalysisCorrelative studies
OTHERPatient ObservationUndergo observation

Timeline

Start date
2017-11-01
Primary completion
2027-09-15
Completion
2027-09-15
First posted
2018-02-01
Last updated
2025-10-08

Locations

590 sites across 4 countries: United States, Puerto Rico, Saudi Arabia, South Korea

Regulatory

Source: ClinicalTrials.gov record NCT03418961. Inclusion in this directory is not an endorsement.