Pilot Study of an NTproBNP Guided Strategy of Cardioprotection

Breast Cancer Clinical Trial

— NTproBNP-Guide  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04737265
• Other study ID #: UPCC 25920
• Secondary ID: R21HL152148
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 18, 2021
• Est. completion date: May 2025

Study information

• Verified date: November 2023
• Source: Abramson Cancer Center at Penn Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 101
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cardiomyopathies
• Cardiotoxicity
• Heart Failure
• Lymphoma
• Toxicity Due to Chemotherapy

Intervention

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.

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California
United States	Abramson Cancer Center at University of Pennsylvania	Philadelphia	Pennsylvania
United States	Chester County Hospital	West Chester	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Abramson Cancer Center at Penn Medicine	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in diastolic function on echo	Change in E/e' by echo	12 months
Other	Change in longitudinal strain	Change in global longitudinal strain by echocardiogram	12 months
Other	Change in circumferential strain	Change in circumferential strain by echocardiogram	12 months
Other	Change in high sensitivity troponin (hsTnT)	Change in hsTnT measured in batches from banked samples	12 months
Other	Change in Growth Differentiation Factor 15 (GDF-15)	Change in GDF-15 measured in batches from banked samples	12 months
Other	Change in myeloperoxidase (MPO)	Change in MPO measured in batches from banked samples	12 months
Other	Change in NTproBNP (post hoc batch analysis)	Change in NTproBNP measured in batches from banked samples for all patients on both arms	12 months
Other	Change in patient reported activity level	Change in total weekly leisure activity in METS (assessed by GODIN Leisure Time Exercise Questionnaire)	12 months
Other	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
Other	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
Other	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
Other	Change in patient reported adverse events	Change in NCI Patient Reported Outcomes - Common Terms and Criteria for Adverse Events (PRO CTCAE).	12 months
Other	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
Primary	Recruitment Rate	percent of eligible patients who are randomized	At baseline
Primary	Retention rate	percent of randomized patients who complete the study per protocol	Through study completion (expected to be 1 year)
Primary	Adherence rate	percent of study activities completed in window	Through study completion (expected to be 1 year)
Primary	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)
Primary	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)
Primary	Incidence of Adverse Events	Rate of Grade 2 or higher adverse events by CTCAEv5.0	12 months
Secondary	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)
Secondary	Change in Left ventricular ejection fraction (LVEF) by Echocardiogram	Change in core-lab quantitated left ventricular ejection fraction	12 months
Secondary	Incidence of cardiotoxicity	Incidence of cardiotoxicity defined as LVEF decline of at least 10% to less than 50%	12 months
Secondary	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
Secondary	Frequency of cancer treatment interruptions	Frequency of cancer treatment interruptions due to cardiotoxicity	Through study completion (expected to be 1 year)