Pilot Study of an NTproBNP Guided Strategy of Cardioprotection (NTproBNP-Guide)

A Randomized, Open Label Pilot Trial of a Biomarker Guided Strategy of Cardioprotection in Patients With Lymphoma or Breast Cancer Treated With Anthracyclines

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Lymphoma; Breast Cancer; Cardiomyopathies; Cardiotoxicity; Toxicity Due to Chemotherapy
• Intervention / Treatment: Other: Biomarker Guided Intervention

Detailed Description

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
• Enrollment (Actual): 101
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center at University of Pennsylvania
    • West Chester, Pennsylvania, United States, 19380
      • Chester County Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of written informed consent and HIPAA authorization
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, ≥ 18 years of age
• Diagnosed with breast cancer or lymphoma (any subtype), planned to receive an anthracycline based chemotherapy regimen. Patients may be enrolled up to their first dose of anthracycline even if they have already received other chemotherapeutic or targeted agents as part of neo-adjuvant or adjuvant systemic therapy.

Exclusion Criteria:

• Diagnosed with Stage IV breast cancer
• Uncontrolled blood pressure defined by SBP > 180mmHg on two or more occasions and taking three or more antihypertensives within 1 month prior to enrollment.
• Baseline systolic blood pressure < 90mmHg within 1 month prior to enrollment (if multiple blood pressures are available in the medical record within 1 month prior to enrollment, the average SBP will be considered)
• Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with some anti-hypertensives, including angiotensin receptor blockers. All females of childbearing potential must have a blood test or urine study within 10 days prior to enrollment to rule out pregnancy. All females of childbearing potential must be strongly advised to use accepted and effective methods of contraception or to abstain from sexual intercourse for the duration of their participation in the study. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Patient with prior or concurrent malignancy whose natural history of treatment, in the opinion of the investigator, has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Patient must not have any of the following
• Severe hepatic impairment, defined as serum bilirubin > ULN, or AST or ALT > 5.0 ULN on most recent labs prior to enrollment. Results of serum bilirubin, AST, and ALT must be checked for screening if no results available in the EMR within 28 days prior to enrollment.
• end-stage renal failure on dialysis
• hyperkalemia with a potassium > 5.5 mEq/l on most recent labs prior to enrollment. Serum potassium must be checked for screening if no results available in the EMR within 28 days prior to enrollment.
• a history of kidney transplant
• an eGFR < 30 ml/min/1.73m2 at most recent check prior to enrollment. Creatinine must be checked for screening if no results available in the EMR within 28 days prior to enrollment
• cardiogenic shock
• decompensated heart failure requiring the use of IV inotropic therapy
• Non-English speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biomarker Guided Arm; NTproBNP will be monitored serially prior to start of anthracycline based chemotherapy, at each cycle of anthracycline based chemotherapy, and at 3 month intervals for a total of 12 months. Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and at standardized intervals at 3, 6, 9, and 12 months following initiation of Anthracycline chemotherapy.	Other: Biomarker Guided Intervention; 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.
No Intervention: Usual Care; NTproBNP will not be monitored while patients are on study unless clinically indicated. Clinical, echocardiographic, and biomarker data will be collected on all patients at baseline and at standardized intervals at 3, 6, 9, and 12 months following initiation of Anthracycline chemotherapy. Biomarker data will also be collected at each cycle of Anthracycline chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment Rate	percent of eligible patients who are randomized	At baseline
Retention rate	percent of randomized patients who complete the study per protocol	Through study completion (expected to be 1 year)
Adherence rate	percent of study activities completed in window	Through study completion (expected to be 1 year)
Compliance rate	Compliance by PROMIS Scale v1.0 for patients in the biomarker guided arm initiated on heart failure medications	Through study completion (expected to be 1 year)
Maximum tolerated dose	Maximum tolerated dosage of neurohormonal antagonist medications for patients in the biomarker-guided arm with NTproBNP above upper limit of normal	Through study completion (expected to be 1 year)
Incidence of Adverse Events	Rate of Grade 2 or higher adverse events by CTCAEv5.0	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NTproBNP	Change in clinically measured NTproBNP following initiation of neurohormonal antagonists in patients with NTproBNP above upper limit of normal in the biomarker guided arm	Through study completion (expected to be 1 year)
Change in Left ventricular ejection fraction (LVEF) by Echocardiogram	Change in core-lab quantitated left ventricular ejection fraction	12 months
Incidence of cardiotoxicity	Incidence of cardiotoxicity defined as LVEF decline of at least 10% to less than 50%	12 months
Incidence of Hear Failure (HF)	Incidence of new or worsened clinical heart failure, defined as urgent or new office or emergency department visit or hospitalization for HF, adjudicated by a clinical events committee	12 months
Frequency of cancer treatment interruptions	Frequency of cancer treatment interruptions due to cardiotoxicity	Through study completion (expected to be 1 year)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in diastolic function on echo	Change in E/e' by echo	12 months
Change in longitudinal strain	Change in global longitudinal strain by echocardiogram	12 months
Change in circumferential strain	Change in circumferential strain by echocardiogram	12 months
Change in high sensitivity troponin (hsTnT)	Change in hsTnT measured in batches from banked samples	12 months
Change in Growth Differentiation Factor 15 (GDF-15)	Change in GDF-15 measured in batches from banked samples	12 months
Change in myeloperoxidase (MPO)	Change in MPO measured in batches from banked samples	12 months
Change in NTproBNP (post hoc batch analysis)	Change in NTproBNP measured in batches from banked samples for all patients on both arms	12 months
Change in patient reported activity level	Change in total weekly leisure activity in METS (assessed by GODIN Leisure Time Exercise Questionnaire)	12 months
Change in patient reported symptoms	Change in MD Anderson Symptoms Inventory - Heart Failure (MDASI-HF). Higher scores indicate increased symptom severity or symptom distress.	12 months
Change in patient reported fatigue	Change in Patient Reported Outomes Information System (PROMIS) Fatigue Score. A higher score corresponds to higher levels of reported fatigue.	12 months
Change in patient reported quality of life	Change in Patient Reported Outomes Information System (PROMIS) Global Health score. Higher scores indicate a healthier patient.	12 months
Change in patient reported adverse events	Change in NCI Patient Reported Outcomes - Common Terms and Criteria for Adverse Events (PRO CTCAE).	12 months
Incidence of treatment interruptions in administration of anthracycline chemotherapy	Incidence of anthracycline chemotherapy being held or discontinued secondary to side effects or toxicity	12 months

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Bonnie Ky, MD, MSCE, Perelman School of Medicine at the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2021
• Primary Completion (Actual): February 5, 2025
• Study Completion (Actual): February 5, 2025

Study Registration Dates

• First Submitted: January 28, 2021
• First Submitted That Met QC Criteria: February 2, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Cardiomyopathy; Cardio-Oncology; Risk-Guided Intervention; Cardiotoxicity of Chemotherapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Neoplasms by Site; Neoplasms; Heart Diseases; Immune System Diseases; Neoplasms by Histologic Type; Chemically-Induced Disorders; Skin Diseases; Breast Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Breast Neoplasms; Lymphoma; Cardiomyopathies; Cardiotoxicity
• Other Study ID Numbers: UPCC 25920; R21HL152148 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No