Stress Test in Detecting Heart Damage in Premenopausal Women With Stage I-III Breast Cancer

Completed

• Conditions: Anatomic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Premenopausal; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8
• Interventions: Biological: Adenosine; Procedure: Magnetic Resonance Imaging; Drug: Regadenoson; Procedure: Stress Management Therapy

• Registration Number: NCT03505736
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

This pilot trial studies how well a stress test works in detecting heart damage in premenopausal women with stage I-III breast cancer. Giving a stress test with adenosine or regadenoson and cardiovascular magnetic resonance imaging may help doctors detect heart damage caused by breast cancer treatments including chemotherapy and aromatase inhibitors.

Detailed Description

PRIMARY OBJECTIVES:

I. To describe decrements in left ventricular myocardial microcirculatory perfusion reserve in premenopausal women treated with an aromatase inhibitor for high-risk hormone receptor-positive breast cancer and in premenopausal women treated without an aromatase inhibitor for triple negative breast cancer over three to six months of in the first 24 months on an aromatase inhibitor or after cessation of chemotherapy, respectively.

SECONDARY OBJECTIVES:

I. To describe changes between the cohorts with hormone receptor-positive and triple negative breast cancer in other measures of cardiovascular function as measured by myocardial rest T1 (myocardial fibrosis burden) and left ventricular ejection fraction (LVEF) measured noninvasively with cardiovascular magnetic resonance (CMR) imaging over three to six months.

II. To describe the relationship of clinical and demographic variables in relation to their potential contribution to changes in left ventricular myocardial microcirculatory perfusion reserve over three to six months in both groups.

III. To study the overall feasibility of accruing and retaining premenopausal women with stage I-III breast cancer in a trial using adenosine stress CMR to assess myocardial perfusion reserve (MPR) and other parameters of cardiovascular health.

OUTLINE:

Within 2 years of initiating anti-estrogen therapy or 2 years after completing chemotherapy, participants undergo a stress test which consists of receiving adenosine intravenously (IV) over 1-5 minutes or regadenoson IV over 2 minutes and then undergoing CMR imaging over 45-60 minutes at baseline and then 3-6 months later.

After completion of study, participants are followed up at 30 days.

Study Timeline

• Study First Submitted: 2018-04-12
• Study First Submitted QC: 2018-04-12
• Study First Posted: 2018-04-23
• Study Start: 2018-06-21
• Status Verified: 2020-03
• Primary Completion: 2020-03-05
• Study Completion: 2020-03-05
• Last Update Submitted: 2020-03-25
• Last Update Posted: 2020-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 25

Inclusion Criteria

• Women who were premenopausal at the time of breast cancer diagnosis; (premenopausal is defined as per National Comprehensive Cancer Network (NCCN) criteria
• Breast cancer treatment is within three years of initiating anti-estrogen therapy and includes medically or surgically induced menopause (HR-positive tumor) or three years of completing chemotherapy (HR-negative tumor)
• Diagnosed with stage I-III breast cancer OR with metastatic breast cancer and receiving ovarian suppression function and aromatase inhibitors as their first non-chemotherapy regimen in the metastatic setting (can include CDK inhibitor with aromatase inhibitor)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document (either directly or via a legally authorized representative)

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Exclusion Criteria

• Women with human epidermal growth factor-2 (HER2) positive breast cancer would be excluded from this pilot given the confounding issue of the cardiotoxicity associated with HER2-directed therapies.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to adenosine (or regadenoson for those with history of asthma or chronic obstructive pulmonary disease [COPD])
• Those with contraindications for MRI such as some breast expanders, ferromagnetic cerebral aneurysm clips or other intracranial metal, pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; a pregnancy test is required, unless the patient has undergone either a bilateral oophorectomy, hysterectomy or both
• Coronary revascularization in the past 6 months or known severe multi-vessel coronary artery disease (CAD) previously determined to be not amenable to mechanical intervention
• Ongoing, unrelieved symptoms thought to represent cardiac ischemia and requiring immediate cardiac catheterization

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Diagnostic (stress test)	Adenosine	Within 2 years of initiating anti-estrogen therapy or 2 years after completing chemotherapy, participants undergo a stress test which consists of receiving adenosine IV over 1-5 minutes or regadenoson IV over 2 minutes and then undergoing CMR imaging over 45-60 minutes at baseline, and again 3-6 months later.
Diagnostic (stress test)	Magnetic Resonance Imaging	Within 2 years of initiating anti-estrogen therapy or 2 years after completing chemotherapy, participants undergo a stress test which consists of receiving adenosine IV over 1-5 minutes or regadenoson IV over 2 minutes and then undergoing CMR imaging over 45-60 minutes at baseline, and again 3-6 months later.
Diagnostic (stress test)	Stress Management Therapy	Within 2 years of initiating anti-estrogen therapy or 2 years after completing chemotherapy, participants undergo a stress test which consists of receiving adenosine IV over 1-5 minutes or regadenoson IV over 2 minutes and then undergoing CMR imaging over 45-60 minutes at baseline, and again 3-6 months later.
Diagnostic (stress test)	Regadenoson	Within 2 years of initiating anti-estrogen therapy or 2 years after completing chemotherapy, participants undergo a stress test which consists of receiving adenosine IV over 1-5 minutes or regadenoson IV over 2 minutes and then undergoing CMR imaging over 45-60 minutes at baseline, and again 3-6 months later.

Primary Outcome Measures

Name	Time	Method
Myocardial perfusion reserve index (MPRI)	Baseline and 3-6 months	Will first estimate 95% confidence intervals for each group at each time point as well as for the change from baseline to 3-6-months in each group.

Secondary Outcome Measures

Name	Time	Method
Myocardial rest myocardial fibrosis burden (T1) and left ventricular ejection fraction (LVEF)	Baseline and 3-6 months	Will be used to correlate myocardial perfusion with T1 and myocardial function (LVEF).
Accrual rate defined as based on the number of patients who participate compared to the total number of patients approached	Baseline and 3-6 months	Will capture data for those approached and consenting or declining and any reasons given for declining participation into the study. Will be assessed by estimating counts and percent's and corresponding 95% Clopper-Pearson exact binomial confidence intervals. Will be compared to the total number of patients enrolled.
Retention rate defined the number of patients who are enrolled and complete both assessments	Baseline and 3-6 months	Will be assessed by estimating counts and percent's and corresponding 95% Clopper-Pearson exact binomial confidence intervals. Will be compared to the total number of patients enrolled.
Change in MPRI measures	Baseline to 3-6 months	Change in MPRI measures (overall and within each group) will be compared using 2-sample t-tests for binary variables. Correlations will be estimated between BMI and the change in MPRI measures.

Trial Locations

Locations (1)

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States