Pilot Study of an NTproBNP Guided Strategy of Cardioprotection

NCT04737265 | Completed Phase 1

• 2 other identifiers: UPCC 25920R21HL152148
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Cardiotoxicity; Toxicity Due to Chemotherapy; Breast Cancer; Lymphoma; Cardiomyopathies; Heart Failure

Keywords

Risk-Guided Intervention; Cardiotoxicity of Chemotherapy; Cardio-Oncology; Cardiomyopathy

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• Change in NTproBNP

  Through study completion (expected to be 1 year)

• Change in Left ventricular ejection fraction (LVEF) by Echocardiogram

  12 months

• Incidence of cardiotoxicity

  12 months

• Incidence of Hear Failure (HF)

  12 months

• Frequency of cancer treatment interruptions

  Through study completion (expected to be 1 year)

Other Outcomes (13)

• Change in diastolic function on echo

  12 months

• Change in longitudinal strain

  12 months

• Change in circumferential strain

  12 months

Study Arms (2)

Biomarker Guided Arm

EXPERIMENTAL

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

Usual Care

NO INTERVENTION

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.

Interventions

Biomarker Guided Intervention OTHER

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.

Biomarker Guided Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

Abramson Cancer Center at University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Chester County Hospital

West Chester, Pennsylvania, 19380, United States

Location

Related Publications (1)

• Xia C, Smith AM, Lefebvre B, Jamal FA, Armenian SH, Koropeckyj-Cox D, Zhang L, Liu PP, Landsburg D, Clark AS, Shah PD, Hubbard RA, Huang A, Golec S, Hewitt M, Wilcox NS, Chen Z, Rethy L, Jung W, Ko K, Narayan V, Martei YM, Lang NN, Januzzi JL, Felker GM, Ky B. Biomarker-Guided Cardioprotection for Patients Treated With Anthracyclines: A Randomized Clinical Trial. JAMA Netw Open. 2025 Dec 1;8(12):e2546201. doi: 10.1001/jamanetworkopen.2025.46201.

  PMID: 41335439 DERIVED

MeSH Terms

Conditions

Cardiotoxicity; Breast Neoplasms; Lymphoma; Cardiomyopathies; Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Bonnie Ky, MD, MSCE

  Perelman School of Medicine at the University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Serial monitoring of NTproBNP during chemotherapy will be used to identify high-risk patients in the intervention arm; patients who experience elevations in NTproBNP will be initiated and titrated on a personalized regimen of neurohormonal antagonists. Patients in the usual care arm will not have serial NTproBNP monitoring and will be managed according to usual care.

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 3, 2021
• Study Start: March 18, 2021
• Primary Completion: February 5, 2025
• Study Completion: February 5, 2025
• Last Updated: July 3, 2025

Record last verified: 2025-07

Locations

US (3)