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
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
Study Contact
- Name: Amanda Smith, MA
- Email: amanda.smith4@pennmedicine.upenn.edu
Study Contact Backup
- Name: Bonnie Ky, MD, MSCE
- Phone Number: 215-573-6606
- Email: bonnie.ky@pennmedicine.edu
Study Locations
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California
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Duarte, California, United States, 91010
- City of Hope
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Abramson Cancer Center at University of Pennsylvania
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West Chester, Pennsylvania, United States, 19380
- Chester County Hospital
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / 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. |
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.
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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.
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Recruitment Rate
Time Frame: At baseline
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percent of eligible patients who are randomized
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At baseline
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Retention rate
Time Frame: Through study completion (expected to be 1 year)
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percent of randomized patients who complete the study per protocol
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Through study completion (expected to be 1 year)
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Adherence rate
Time Frame: Through study completion (expected to be 1 year)
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percent of study activities completed in window
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Through study completion (expected to be 1 year)
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Compliance rate
Time Frame: Through study completion (expected to be 1 year)
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Compliance by PROMIS Scale v1.0 for patients in the biomarker guided arm initiated on heart failure medications
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Through study completion (expected to be 1 year)
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Maximum tolerated dose
Time Frame: Through study completion (expected to be 1 year)
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Maximum tolerated dosage of neurohormonal antagonist medications for patients in the biomarker-guided arm with NTproBNP above upper limit of normal
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Through study completion (expected to be 1 year)
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Incidence of Adverse Events
Time Frame: 12 months
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Rate of Grade 2 or higher adverse events by CTCAEv5.0
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12 months
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Change in NTproBNP
Time Frame: Through study completion (expected to be 1 year)
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Change in clinically measured NTproBNP following initiation of neurohormonal antagonists in patients with NTproBNP above upper limit of normal in the biomarker guided arm
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Through study completion (expected to be 1 year)
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Change in Left ventricular ejection fraction (LVEF) by Echocardiogram
Time Frame: 12 months
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Change in core-lab quantitated left ventricular ejection fraction
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12 months
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Incidence of cardiotoxicity
Time Frame: 12 months
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Incidence of cardiotoxicity defined as LVEF decline of at least 10% to less than 50%
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12 months
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Incidence of Hear Failure (HF)
Time Frame: 12 months
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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
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12 months
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Frequency of cancer treatment interruptions
Time Frame: Through study completion (expected to be 1 year)
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Frequency of cancer treatment interruptions due to cardiotoxicity
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Through study completion (expected to be 1 year)
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Other Outcome Measures
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change in diastolic function on echo
Time Frame: 12 months
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Change in E/e' by echo
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12 months
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Change in longitudinal strain
Time Frame: 12 months
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Change in global longitudinal strain by echocardiogram
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12 months
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Change in circumferential strain
Time Frame: 12 months
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Change in circumferential strain by echocardiogram
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12 months
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Change in high sensitivity troponin (hsTnT)
Time Frame: 12 months
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Change in hsTnT measured in batches from banked samples
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12 months
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Change in Growth Differentiation Factor 15 (GDF-15)
Time Frame: 12 months
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Change in GDF-15 measured in batches from banked samples
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12 months
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Change in myeloperoxidase (MPO)
Time Frame: 12 months
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Change in MPO measured in batches from banked samples
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12 months
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Change in NTproBNP (post hoc batch analysis)
Time Frame: 12 months
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Change in NTproBNP measured in batches from banked samples for all patients on both arms
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12 months
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Change in patient reported activity level
Time Frame: 12 months
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Change in total weekly leisure activity in METS (assessed by GODIN Leisure Time Exercise Questionnaire)
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12 months
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Change in patient reported symptoms
Time Frame: 12 months
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Change in MD Anderson Symptoms Inventory - Heart Failure (MDASI-HF).
Higher scores indicate increased symptom severity or symptom distress.
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12 months
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Change in patient reported fatigue
Time Frame: 12 months
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Change in Patient Reported Outomes Information System (PROMIS) Fatigue Score.
A higher score corresponds to higher levels of reported fatigue.
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12 months
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Change in patient reported quality of life
Time Frame: 12 months
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Change in Patient Reported Outomes Information System (PROMIS) Global Health score.
Higher scores indicate a healthier patient.
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12 months
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Change in patient reported adverse events
Time Frame: 12 months
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Change in NCI Patient Reported Outcomes - Common Terms and Criteria for Adverse Events (PRO CTCAE).
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12 months
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Incidence of treatment interruptions in administration of anthracycline chemotherapy
Time Frame: 12 months
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Incidence of anthracycline chemotherapy being held or discontinued secondary to side effects or toxicity
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12 months
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Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
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)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
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
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)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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