Clinical trial NCT04737265: Pilot Study of an NTproBNP Guided Strategy of Cardioprotection
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cardiotoxicity
Toxicity Due to Chemotherapy
Breast Cancer
Lymphoma
Cardiomyopathies
Heart Failure
Keywords: Risk-Guided Intervention
Cardiotoxicity of Chemotherapy
Cardio-Oncology
Cardiomyopathy
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2021-02-03
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment Rate
timeFrame: At baseline
measure: Retention rate
timeFrame: Through study completion (expected to be 1 year)
measure: Adherence rate
timeFrame: Through study completion (expected to be 1 year)
measure: Compliance rate
timeFrame: Through study completion (expected to be 1 year)
measure: Maximum tolerated dose
timeFrame: Through study completion (expected to be 1 year)
measure: Incidence of Adverse Events
timeFrame: 12 months
Secondary outcomes:
measure: Change in NTproBNP
timeFrame: Through study completion (expected to be 1 year)
measure: Change in Left ventricular ejection fraction (LVEF) by Echocardiogram
timeFrame: 12 months
measure: Incidence of cardiotoxicity
timeFrame: 12 months
measure: Incidence of Hear Failure (HF)
timeFrame: 12 months
measure: Frequency of cancer treatment interruptions
timeFrame: Through study completion (expected to be 1 year)
Other outcomes:
measure: Change in diastolic function on echo
timeFrame: 12 months
measure: Change in longitudinal strain
timeFrame: 12 months
measure: Change in circumferential strain
timeFrame: 12 months
measure: Change in high sensitivity troponin (hsTnT)
timeFrame: 12 months
measure: Change in Growth Differentiation Factor 15 (GDF-15)
timeFrame: 12 months
measure: Change in myeloperoxidase (MPO)
timeFrame: 12 months
measure: Change in NTproBNP (post hoc batch analysis)
timeFrame: 12 months
measure: Change in patient reported activity level
timeFrame: 12 months
measure: Change in patient reported symptoms
timeFrame: 12 months
measure: Change in patient reported fatigue
timeFrame: 12 months
measure: Change in patient reported quality of life
timeFrame: 12 months
measure: Change in patient reported adverse events
timeFrame: 12 months
measure: Incidence of treatment interruptions in administration of anthracycline chemotherapy
timeFrame: 12 months
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Philadelphia
country: United States
facility: Abramson Cancer Center at University of Pennsylvania
state: Pennsylvania
city: West Chester
country: United States
facility: Chester County Hospital
state: Pennsylvania
Study officials:
affiliation: Perelman School of Medicine at the University of Pennsylvania
name: Bonnie Ky, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References: