NCT03418961|RecruitingPhase 3DMCFDA Drug

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

SWOG Cancer Research Network ClinicalTrials.gov

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4 other identifiers

S1501UG1CA189974NCI-2016-01047SWOG-S1501

Study Type

interventional

Target

491

Locations

4 countries

Sites

590

Timeline

RegisteredFeb 2018

StartedNov 2017

CompletionSep 2027

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

491

participants targeted

Target at P50-P75 for phase_3

Timeline

16mo left

Started Nov 2017

Longer than P75 for phase_3

Geographic Reach

4 countries

590 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.9 years study duration

Study Progress86%

Nov 2017Sep 2027

Study Start

First participant enrolled

November 1, 2017

Completed

2 months until next milestone

First Submitted

Initial submission to the registry

January 2, 2018

Completed

1 month until next milestone

First Posted

Study publicly available on registry

February 1, 2018

Completed

9.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 15, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 15, 2027

Last Updated

October 8, 2025

Status Verified

October 1, 2025

Enrollment Period

9.9 years

First QC Date

January 2, 2018

Last Update Submit

October 3, 2025

Conditions

Cardiotoxicity HER2/Neu Positive Metastatic Malignant Neoplasm in the Brain Recurrent Breast Carcinoma Stage IV Breast Cancer AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

Time to the first identification of cardiac dysfunction
Real-time, blinded, central echocardiography (ECHO) read as a decrease in the left ventricular ejection fraction (LVEF) of \>= 10 percentage points from baseline to a value of \< 50% OR decrease of LVEF by \>= 5 percentage points from baseline to LVEF \< 50% in those baselines having a baseline LVEF of 50-54%. The distributions of time to cardiac dysfunction will be described using cumulative incidence estimates, with the statistical significance of treatment arm differences assessed by Cox and Fine-Gray regression models with adjustment for stratification factors. Gray's test will also be applied
Up to 108 weeks

Secondary Outcomes (5)

Incidence of adverse events associated with beta blocker treatment
Up to 108 weeks
Rate of first interruption of trastuzumab
Up to 108 weeks
Rate of death
Up to 108 weeks
Time to first occurrence of cardiac event
Up to 108 weeks
Drug adherence
Up to 108 weeks

Study Arms (3)

Arm I (carvedilol)

EXPERIMENTAL

Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive carvedilol PO BID. Courses repeat every 12 weeks for 108 weeks in the absence of disease progression or unacceptable toxicity.

Drug: CarvedilolOther: Laboratory Biomarker Analysis

Arm II (no intervention)

ACTIVE COMPARATOR

Patients not taking beta blocker, ARB, or ACE inhibitor at registration receive no study intervention for up to 108 weeks.

Other: Laboratory Biomarker Analysis

Arm III (observation)

ACTIVE COMPARATOR

Patients undergo observation for up to 108 weeks.

Other: Laboratory Biomarker AnalysisOther: Patient Observation

Interventions

CarvedilolDRUG

Given PO

Also known as: Coreg

Arm I (carvedilol)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (carvedilol)Arm II (no intervention)Arm III (observation)

Patient ObservationOTHER

Undergo observation

Also known as: Active Surveillance, deferred therapy, expectant management, observation, Watchful Waiting

Arm III (observation)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

STEP 1 REGISTRATION
Patients must:
Have metastatic breast cancer, AND
Be initiating within 11 calendar days of Step 1 Registration OR be continuing trastuzumab-based HER-2 targeted therapy without concurrent anthracyclines, AND
Be receiving the trastuzumab-based HER-2 targeted therapy for metastatic disease in first, second, third-, or fourth-line setting. Patients may have brain metastasis. There is no limit for number of doses of HER-2 targeted therapy prior to registration.
Examples of eligible HER-2 targeted therapy:
Trastuzumab or a trastuzumab biosimilar
Trastuzumab + chemotherapy or hormonal therapy
Trastuzumab + other HER-2 targeted agent with or without chemotherapy (such as pertuzumab, lapatinib, and tucatinib)
Ado-trastuzumab (Kadcyla®)
Fam-trastuzumab deruxtecan (Enhertu) NOTE: Patients on lapatinib without trastuzumab are not eligible. Planned treatment with concurrent HER-2 targeted therapy and anthracyclines is not permitted.
Patients must be at increased risk for cardiotoxicity defined by at least one of the following:
Previous anthracycline exposure OR
or more of the following risk factors for heart disease:
LVEF 50-54% by local ECHO read\*
+27 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

SWOG Cancer Research Networklead
National Cancer Institute (NCI)collaborator

Study Sites (590)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

SUSPENDED

Alaska Breast Care and Surgery LLC