Doxorubicin Adverse ReactionNCT03505164
The Role of suPAR Biomarker in Blood Samples of Breast Cancer Patients During and Post Doxorubicin Chemotherapy: Causative vs. Predictor
An observational study of Doxorubicin Adverse Reaction and Cardiomyopathies, Secondary, run by Rush University Medical Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years, women only
- Conditions the study is for
- Doxorubicin Adverse Reaction, Cardiomyopathies, Secondary, Breast Cancer
- How many people
- 42 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Jan 2017to 6 Jul 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- Women only
- No healthy volunteers
- Adult
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.
Who may be able to join
- 18 - 64 years
- Undergoing chemotherapy in the Rush cancer center with a plan for doxorubicin (Adriamycin®) chemotherapy.
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Rush University Medical Center
Chicago, Illinois, 60612
Rush Oak Park Hospital
Oak Park, Illinois, 60304
About this study
Official title: The Role of suPAR in Doxorubicin Induced Cardiomyopathy in Breast Cancer Patients: Causative vs. Predictor
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.
Read more
- 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.
Read the detailed description
- Hypothesis 1: Higher suPAR at baseline will predispose to DOX-induced cardiomyopathy to be observed by histology in mouse models, and tested using LVEF (Left Ventricular Ejection Fraction) assessment, and surrogate cardiovascular outcome measures as described in humans.
- Hypothesis 2: suPAR is a marker of DOX-induced cardiomyopathy after exposure to DOX, to be observed by histology in mouse models, and tested using surrogate cardiovascular outcome measures as described in humans.
- Patients meeting outlined eligibility criteria are identified by breast cancer physicians working in the Rush Cancer Center. After eligibility is verified, patients are approached by the study coordinators or research fellow to discuss participation in the trial while patients were being seen by their provider within the cancer center and given the informed consent form for review. Patients are contacted approximately one week later to answer questions and plan for baseline visit if interested in enrolling.
- After signing the informed consent form, patients are officially enrolled. The research nurse, study coordinator, or research fellow will conduct research visits at each of the six study time points outlined in the protocol: pre-chemo, post-2 cycles of doxorubicin, post-4 cycles of doxorubicin, 3 months post-doxorubicin, 6 month post-doxorubicin and 12 months post-doxorubin
- Each study visit consists of collecting lab work via blood draw as detailed in the protocol as well as an echocardiogram performed with strain.
- Results from each test are collected, reviewed by the PI and documented in the patient's study binder.
- Preliminary human results have not been analyzed at this time as there is currently insufficient data collected.
In the laboratory approach of the study, the investigators aimed to establish the role of suPAR in DOX induced cardiomyopathy. The risk for DOX induced cardiomyopathy is known to increase with an increase of the accumulative dose. The investigators therefore used two doses of DOX. One group of mice received weekly injections of DOX at 3mg/kg bodyweight for 6 week (accumulative dose of 18mg/kg: DOX18) whereas another group received an accumulative dose of 25mg/kg bodyweight (DOX25: 5 weeks, at 5 mg/kg bodyweight). Blood samples were taken before the first injection, in the middle of treatment and at the end of treatment or at the day of sacrifice. The bodyweight of the animals was constantly monitored throughout the study.
At time of sacrifice, the heart weight and tibia length of the mice were quantified and cells were isolated to determine cellular levels of reactive oxygen species (ROS), contractility and Ca handling properties.
DOX induced cardiomyopathy can manifest years after treatment. Tissue samples from hearts of the DOX18 and DOX25 treatment group were obtained and quantitative PCR (Polymerase Chain Reaction amplification) of the ventricular tissue will help us determine the changes in protein expression and cellular signaling that underlie these DOX induced changes in cellular function.
Blood samples obtained from the DOX18 and DOX25 mice will be analyzed for their level of suPAR to determine changes in suPAR over the duration of treatment and potential correlations of [suPAR] with the degree of cardiac dysfunction.
The data collected will be analyzed using a descriptive analysis with means and standard deviations for continuous variables and percentages for categorical variables. A paired t-test comparing the pre-post difference will be used to compare the differences in the groups comparing pre to post measures of myocardial damage based on histology for mouse models, and LVEF (Left Ventricular Ejection Fraction) for human data. Analysis will be performed using SAS (statistical analysis software).
The expected results from the data collected in this study aim to both gain an understanding of and describe the relationship of various covariates to primary outcomes.
It is expected to have 50 participants by the study end date. There is a trained team working on the study, insuring quality of data gathering, recruitment and enrollment of patients.
- Keywords
- Doxorubicin, suPAR, Cardiomyopathy, Heart Failure, Breast Cancer
- Medical subject headings
- Cardiomyopathies, Breast Neoplasms, Heart Failure
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2018
- Study start17 Jan 2017
- Primary completion6 Jul 2020
- Study completion6 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Doxorubicin Adverse ReactionStudies of the same condition, open and under way.
- More trials run by Rush University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tochukwu Okwuosa, Rush University Medical Center
- Investigators
- Tochi Okwuosa, DO, FACC, Principal investigator, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03505164
- Sponsor's protocol ID
- 16022426
- Status last verified
- Apr 2021
- First submitted
- 31 Aug 2017
- Last updated
- 27 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of suPAR in Doxorubicin Induced Cardiomyopathy in Breast Cancer Patients: Causative vs. Predictor
- ClinicalTrials.gov ID
- NCT03505164
- Acronym / sponsor ID
- 16022426
- Keywords
- Doxorubicin, suPAR, Cardiomyopathy, Heart Failure, Breast Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Study start
- 17 Jan 2017 (actual)
- Primary completion
- 6 Jul 2020 (actual)
- Study completion
- 6 Jul 2020 (actual)
- First posted
- 23 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- Hypothesis 1: Higher suPAR at baseline will predispose to DOX-induced cardiomyopathy to be observed by histology in mouse models, and tested using LVEF (Left Ventricular Ejection Fraction) assessment, and surrogate cardiovascular outcome measures as described in humans.
- Hypothesis 2: suPAR is a marker of DOX-induced cardiomyopathy after exposure to DOX, to be observed by histology in mouse models, and tested using surrogate cardiovascular outcome measures as described in humans.
- Patients meeting outlined eligibility criteria are identified by breast cancer physicians working in the Rush Cancer Center. After eligibility is verified, patients are approached by the study coordinators or research fellow to discuss participation in the trial while patients were being seen by their provider within the cancer center and given the informed consent form for review. Patients are contacted approximately one week later to answer questions and plan for baseline visit if interested in enrolling.
- After signing the informed consent form, patients are officially enrolled. The research nurse, study coordinator, or research fellow will conduct research visits at each of the six study time points outlined in the protocol: pre-chemo, post-2 cycles of doxorubicin, post-4 cycles of doxorubicin, 3 months post-doxorubicin, 6 month post-doxorubicin and 12 months post-doxorubin
- Each study visit consists of collecting lab work via blood draw as detailed in the protocol as well as an echocardiogram performed with strain.
- Results from each test are collected, reviewed by the PI and documented in the patient's study binder.
- Preliminary human results have not been analyzed at this time as there is currently insufficient data collected.
In the laboratory approach of the study, the investigators aimed to establish the role of suPAR in DOX induced cardiomyopathy. The risk for DOX induced cardiomyopathy is known to increase with an increase of the accumulative dose. The investigators therefore used two doses of DOX. One group of mice received weekly injections of DOX at 3mg/kg bodyweight for 6 week (accumulative dose of 18mg/kg: DOX18) whereas another group received an accumulative dose of 25mg/kg bodyweight (DOX25: 5 weeks, at 5 mg/kg bodyweight). Blood samples were taken before the first injection, in the middle of treatment and at the end of treatment or at the day of sacrifice. The bodyweight of the animals was constantly monitored throughout the study.
At time of sacrifice, the heart weight and tibia length of the mice were quantified and cells were isolated to determine cellular levels of reactive oxygen species (ROS), contractility and Ca handling properties.
DOX induced cardiomyopathy can manifest years after treatment. Tissue samples from hearts of the DOX18 and DOX25 treatment group were obtained and quantitative PCR (Polymerase Chain Reaction amplification) of the ventricular tissue will help us determine the changes in protein expression and cellular signaling that underlie these DOX induced changes in cellular function.
Blood samples obtained from the DOX18 and DOX25 mice will be analyzed for their level of suPAR to determine changes in suPAR over the duration of treatment and potential correlations of [suPAR] with the degree of cardiac dysfunction.
The data collected will be analyzed using a descriptive analysis with means and standard deviations for continuous variables and percentages for categorical variables. A paired t-test comparing the pre-post difference will be used to compare the differences in the groups comparing pre to post measures of myocardial damage based on histology for mouse models, and LVEF (Left Ventricular Ejection Fraction) for human data. Analysis will be performed using SAS (statistical analysis software).
The expected results from the data collected in this study aim to both gain an understanding of and describe the relationship of various covariates to primary outcomes.
It is expected to have 50 participants by the study end date. There is a trained team working on the study, insuring quality of data gathering, recruitment and enrollment of patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 64 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (2 listed)
- 18 - 64 years
- Undergoing chemotherapy in the Rush cancer center with a plan for doxorubicin (Adriamycin®) chemotherapy.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Causality relationship between the suPAR blood level and doxorubicin-induced cardiomyopathy
Time frame: 12 months
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.
Predictive relationship between suPAR blood level and doxorubicin-induced cardiomyopathy
Time frame: 12 months
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tochi Okwuosa, DO, FACC principal investigator
Rush University Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Doxorubicin Adverse Reaction and Cardiomyopathies, Secondary, run by Rush University Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Causality relationship between the suPAR blood level and doxorubicin-induced cardiomyopathy (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2021.