Investigators will evaluate the safety and feasibility of a biomarker-guided cardioprotection strategy using NTproBNP, as compared to usual care, in breast cancer and lymphoma patients treated with anthracyclines.
This is a randomized, open-label pilot trial of a biomarker-guided strategy using NT-proBNP to identify and treat patients with a high risk of cancer therapy-related cardiotoxicity. Patients will be enrolled and randomized prior to initiation of anthracycline-based therapy and followed for 12 months with blood samples, echocardiography, and patient reported outcomes surveys. The overall hypothesis is that a biomarker guided treatment strategy that initiates neurohormonal antagonists in breast cancer or lymphoma patients who have increases in NT-proBNP prior to, during, or after anthracyclines will be feasible, well-tolerated, and result in attenuation of cardiotoxicity, compared to standard care.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
108
NTproBNP above the upper limit of normal will trigger the initiation of heart failure therapy with counseling from a study investigator based on protocol specified algorithm.
City of Hope
Duarte, California, United States
Abramson Cancer Center at University of Pennsylvania
Philadelphia, Pennsylvania, United States
Chester County Hospital
West Chester, Pennsylvania, United States
Recruitment Rate
percent of patients approached about the study who provided consent
Time frame: At baseline
Retention Rate
percent of randomized patients who complete the study per protocol
Time frame: Through study completion (expected to be 1 year)
Compliance Rate
Compliance by Patient Reported Outcomes Information System (PROMIS) Scale v1.0 for patients in the biomarker guided arm initiated on heart failure medications. A higher PROMIS compliance score indicates better compliance with medications (score ranges from 9 - 45).
Time frame: Through study completion (expected to be 1 year)
Maximum Dose
Maximum dose (mg) of neurohormonal antagonist therapy for participants in the intervention arm who initiated neurohormonal therapy for NTproBNP elevation across all study timepoints. Please note, due to numeric validation requirement, the max dose for combination drugs reported below is the max dose for the component in our algorithm (e.g. valsartan-hydrochlorothiazide is reported below as 325, which is the max dose of valsartan).
Time frame: Through study completion (expected to be 1 year)
Incidence of Adverse Events
Number of patients that had at least one targeted AE of grade 3 or higher at any time on study.
Time frame: 12 months
Change in NTproBNP
Change in estimated core lab measured NTproBNP by group. GEE model adjusted for baseline values and time since anthracycline initiation, modeled with spline function. NTproBNP is a hormone released when the heart is under stress. Concentrations greater than 125 pg/ml are considered to be elevated.
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Time frame: Through study completion (1 year)
Change in Left Ventricular Ejection Fraction (LVEF)
Change in core-lab quantitated LVEF by echocardiogram from baseline. GEE model adjusted for baseline values and time since anthracycline initiation, modeled with spline function. LVEF is a measurement of how much blood the heart pumps out with each beat. It is calculated by dividing the volume of blood ejected with each beat divided the volume of blood in the heart, multiplied by 100 and reported as a percentage. An LVEF of less than 50% is considered abnormal.
Time frame: 12 months
Incidence of Cardiotoxicity
Incidence of cardiotoxicity defined as LVEF decline of at least 10% to less than 50%
Time frame: 12 months
Incidence of Heart Failure (HF)
Incidence of new or worsened clinical heart failure, defined as urgent or new office or emergency department visit or hospitalization for adjudicated heart failure.
Time frame: 12 months
Frequency of Cancer Treatment Interruptions
Frequency of cancer treatment interruptions (holds or early discontinuations)
Time frame: Through study completion (expected to be 1 year)