The Role of suPAR Biomarker in Blood Samples of Breast Cancer Patients During and Post Doxorubicin Chemotherapy: Causative vs. Predictor

NCT03505164 | Completed

• 1 other identifier: 16022426
• Study Type: observational
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

This study looks to find a causative or predictive aspect of the suPAR biomarker for heart failure in breast cancer patients receiving Doxorubicin drug chemo regimen. suPAR is a circulating protein which can be found in blood and/or urine and is associated with both kidney and heart disease.

• Hypothesis 1: Higher suPAR at baseline will predispose to Doxorubicin-induced cardiomyopathy or heart failure, observed by histology (under the microscope and other lab techniques) in mouse models, and tested using heart ultrasound techniques in humans.
• Hypothesis 2: suPAR is a marker of Doxorubicin-induced cardiomyopathy or heart failure after exposure to Doxorubicin, observed by histology (under the microscope and other lab techniques) in mouse models, and tested in humans. The study will look at suPAR's association with three other biomarkers called troponin, B-Type Natriuretic Peptide (BNP) and C- Reactive Protein (CRP) that are also associated with heart disease. In this study, the patient will have blood drawn as a routine part of the cancer treatment. That is prior to starting the cancer therapy, then after the first 2 and last 2 doxorubicin cycles (4 cycles altogether); as well as at 3, 6, \& 12 months after doxorubicin treatment. (6 Visits in total) The patient will also have an echocardiogram (echo, heart ultrasound) at each of these time points. The first of the six study echos is considered part of the routine care.

Conditions

Doxorubicin Adverse Reaction; Cardiomyopathies, Secondary; Breast Cancer

Keywords

Doxorubicin; suPAR; Cardiomyopathy; Heart Failure; Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Causality relationship between the suPAR blood level and doxorubicin-induced cardiomyopathy

  A blood draw will be done at baseline for all participants. The blood samples will be processed by Centrifugation, to separate the plasma, and the suPAR level measured using ELISA technique, to stratify the participants that have a higher or normal baseline. Although there is no current consensus regarding normal suPAR blood level, a level of 3000 pg/mL is considered a high level. Higher baseline blood level of suPAR, will predispose patients with breast cancer undergoing chemo regimen containing doxorubicin, to develop heart toxicity (heart failure or cardiomyopathy). Heart failure or Cardiomyopathy will be diagnosed by the clinical evaluation with signs and symptoms, LVEF (Left Ventricular Ejection Fraction) with echocardiograms (heart ultrasound), and surrogate cardiovascular outcome measures as described in humans, and tissue visualization and histology in mouse models, with various staining techniques, whether it was H\&E staining, or other immunological staining.

  12 months

• Predictive relationship between suPAR blood level and doxorubicin-induced cardiomyopathy

  A blood draw will be done at baseline for all participants. The blood samples will be processed by Centrifugation to separate the plasma, and the suPAR level measured using ELISA technique, to stratify the participants having a higher or normal baseline. Although there is no current consensus regarding normal suPAR blood level, a level less than 3000 pg/mL is considered a normal level. A normal baseline blood level of suPAR, with progressive elevation following doxorubicin exposure, along with other blood markers for heart failure, will be considered as a predictive marker for doxorubicin-induced cardiomyopathy. Heart failure or Cardiomyopathy will be diagnosed by the clinical evaluation with signs and symptoms, LVEF (Left Ventricular Ejection Fraction) with echocardiograms (heart ultrasound), and surrogate cardiovascular outcome measures as described in humans, and tissue visualization and histology in mouse models using H\&E staining, or other immunological staining techniques.

  12 months

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Female patients aged between 18 and 64, recently diagnosed with non metastatic breast cancer, and will be receiving doxorubicin containing chemo regimen. All patients are being treated at Rush University Medical Center, Chicago, IL, and Rush Oak Park Hospital, Oak Park, IL.

You may qualify if:

• years
• Undergoing chemotherapy in the Rush cancer center with a plan for doxorubicin (Adriamycin®) chemotherapy.

You may not qualify if:

• Patients with metastatic breast cancer - complicated chemotherapy regimens, higher mortality risk
• HER2 (human epidermal growth factor receptor 2) positive breast cancer patients planned for trastuzumab therapy
• Patients with baseline cardiomyopathy (reduced LVEF: less than 50%)
• Patients with prior cardiovascular history of myocardial infarction (MI), angina, Congestive Heart Disease (CHD) death, coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) including percutaneous transluminal coronary angioplasty (PTCA) and end-stage renal disease (ESRD), atrial fibrillation prior to cancer diagnosis
• Atrial fibrillation noted on baseline ECG

Sponsors & Collaborators

• Rush University Medical Center: lead

Study Sites (2)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Rush Oak Park Hospital

Oak Park, Illinois, 60304, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples are put in a Centrifugation machine to separate the plasma. The plasma is then kept in -70 to -80 degrees Fahrenheit. Each sample will be studied for suPAR levels.

MeSH Terms

Conditions

Cardiomyopathies; Breast Neoplasms; Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Tochi Okwuosa, DO, FACC

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Tochukwu M. Okwuosa, DO, FACC, Assistant Professor of Medicine and Cardiology, Director of Cardio-Onc Services, Principal Investigator in the suPAR pilot study.

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: April 23, 2018
• Study Start: January 17, 2017
• Primary Completion: July 6, 2020
• Study Completion: July 6, 2020
• Last Updated: April 27, 2021

Record last verified: 2021-04

Locations

US (2)