Breast CancerNCT01173341
Cardiotoxicity of Cancer Therapy (CCT)
An observational study of Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
The objective of this study is to define the clinical significance of mechanistic biomarkers (including Neuregulin-1Beta) and novel echocardiographic measures of cardiac function in predicting the incident risk of cancer therapy cardiotoxicity. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Echocardiography, Blood Collection and Symptoms Questionnaire
- How many people
- 700 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Apr 2037
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Subjects with breast cancer will enter the cohort prior to chemotherapy initiation and be evaluated at baseline and at regular intervals during the first approximately 15 months after chemotherapy is initiated. Patients will have study visits at 2 years, 3 years, 5, years, 7 years, 9 years, 11 years, 13 years, and 15 years following initiation of cancer therapy.
Who may be able to join
- Age 18 years or older
- HER-2 positive breast cancer designated to receive trastuzumab chemotherapy with or without prior exposure to anthracycline-based chemotherapy
- Non-HER-2 positive breast cancer designated to receive treatment with an anthracycline-containing regimen
Who cannot join
- Other contraindications to trastuzumab or anthracycline chemotherapy.
- Vulnerable populations
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Cardiotoxicity of Cancer Therapy: Mechanisms and Predictors
The objective of this study is to define the clinical significance of mechanistic biomarkers (including Neuregulin-1Beta) and novel echocardiographic measures of cardiac function in predicting the incident risk of cancer therapy cardiotoxicity.
Read the detailed description
The overall study objectives are:
- To determine the longitudinal relationships between circulating markers, such as Neuregulin (NRG)-1Beta levels and incident risk of adverse cardiovascular outcomes in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that a sustained increase in NRG-1Beta, indicative of enhanced cardiac stress with exposure to chemotherapeutic agents, is predictive of an increased risk of cardiac dysfunction and heart failure.
- To study the single nucleotide polymorphism (SNP)/haplotype variation in pathways of interest, such as the Neuregulin/Epidermal Growth Factor (ErbB) signaling pathway, on incident risk of adverse cardiovascular outcomes. We hypothesize that there will be SNP/haplotypes variations that are associated with incident cardiovascular outcomes.
- To determine the longitudinal relationships between novel echocardiographic measures, such as strain and strain rate and incident cardiac dysfunction in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that early declines in strain and strain rate are predictive of an increased risk of future cardiac dysfunction and heart failure.
- To explore the changes in biomarkers such as NRG-1Beta levels and the relationships with novel echocardiographic measures of cardiac function.
- To create a biobank as a future resource for additional questions in novel biomarkers and genetics.
- To determine the long-term effects of cancer therapy cardiotoxicity by following patients yearly for 5 years after their exposure to cancer therapy, with the option to extend up to an additional 5 years.
- Conditions
- Breast Cancer
- Being tested
- Echocardiography, Blood Collection, Symptoms Questionnaire
- Keywords
- Chemotherapy-induced cardiotoxicity, Anthracycline, Trastuzumab
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EchocardiographyDiagnostic test
Prior to chemotherapy, prior to and after anthracyclines, every 6 weeks during trastuzumab, and yearly for up to 10 years.
Blood CollectionOther
Drawn at first chemo treatment and periodically during treatment (exact schedule varies with clinically ordered treatment plan), then annually for up to 10 years. Blood is banked for future biomarker testing.
Symptoms QuestionnaireOther
Survey collected at first chemotherapy, periodically during therapy (exact schedule determined by clinically ordered treatment regimen), and annually for up to 10 years.
| Study group | Role | What they receive |
|---|---|---|
| Subgroup 2 | Subgroup2 represents will undergo trastuzumab therapy only Receives: Diagnostic Test: Echocardiography; Other: Blood Collection; Other: Symptoms Questionnaire | |
| Subgroup 1 | Subgroup 1 are anthracycline only treated patients. Receives: Diagnostic Test: Echocardiography; Other: Blood Collection; Other: Symptoms Questionnaire | |
| Subgroup 3 | Subgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines. Receives: Diagnostic Test: Echocardiography; Other: Blood Collection; Other: Symptoms Questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac dysfunction or signs or symptoms of heart failure
Cardiac dysfunction. as defined according to the Cardiac Review and Evaluation Committee (CREC) criteria as a decline in LVEF of 10% to less than 55% without signs or symptoms
Measured: 15 years
Secondary outcomes (1)
Change in quantitated Left Ventricular Ejection Fraction (LVEF)
Change in LVEF over the course of chemotherapy; incident diastolic dysfunction by echocardiography; the combined endpoint of any incident adverse cardiovascular outcome (arrhythmia, heart failure, systolic dysfunction, or diastolic dysfunction by echo)
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionApr 2037 (estimated)
- Study completionApr 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe 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
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bonnie Ky, MD, Principal investigator, Abramson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01173341
- Sponsor's protocol ID
- UPCC 09110
- Status last verified
- Feb 2026
- First submitted
- 29 Jul 2010
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Wilcox NS, Xia C, Yang W, Ko K, Smith AM, Zhang L, Liu PP, Pei L, Baur JA, Cappola TP, Ky B. Early Increases in GDF-15 Are Associated With Declines in Cardiac Function With Breast Cancer Therapy. JACC Adv. 2026 Nov 2:103370. doi: 10.1016/j.jacadv.2026.103370. Online ahead of print.
PubMed 42969899Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan V, Domchek SM, DeMichele A, Shah P, Clark AS, Fox K, Matro J, Bradbury AR, Knollman H, Getz KD, Armenian SH, Januzzi JL, Tang WHW, Liu P, Ky B. Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction. J Am Heart Assoc. 2020 Jan 21;9(2):e014708. doi: 10.1161/JAHA.119.014708. Epub 2020 Jan 21.
PubMed 31959034Upshaw JN, Finkelman B, Hubbard RA, Smith AM, Narayan HK, Arndt L, Domchek S, DeMichele A, Fox K, Shah P, Clark A, Bradbury A, Matro J, Adusumalli S, Carver JR, Ky B. Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy. JACC Cardiovasc Imaging. 2020 Jan;13(1 Pt 2):198-210. doi: 10.1016/j.jcmg.2019.07.018. Epub 2019 Sep 18.
PubMed 31542526Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nunez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F, John Baksi A, O'Regan DP, Rosen SD, Prasad SK, Lara-Pezzi E, Provencio M, Lyon AR, Alonso-Pulpon L, Cook SA, DePalma SR, Barton PJR, Aplenc R, Seidman JG, Ky B, Ware JS, Seidman CE. Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy. Circulation. 2019 Jul 2;140(1):31-41. doi: 10.1161/CIRCULATIONAHA.118.037934. Epub 2019 Apr 16.
PubMed 30987448
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiotoxicity of Cancer Therapy: Mechanisms and Predictors
- ClinicalTrials.gov ID
- NCT01173341
- Acronym / sponsor ID
- UPCC 09110
- Conditions
- Breast Cancer
- Keywords
- Chemotherapy-induced cardiotoxicity, Anthracycline, Trastuzumab
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Jul 2010 (actual)
- Primary completion
- Apr 2037 (estimated)
- Study completion
- Apr 2037 (estimated)
- First posted
- 2 Aug 2010 (estimated)
- 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.
The objective of this study is to define the clinical significance of mechanistic biomarkers (including Neuregulin-1Beta) and novel echocardiographic measures of cardiac function in predicting the incident risk of cancer therapy cardiotoxicity.
Detailed description
The overall study objectives are:
- To determine the longitudinal relationships between circulating markers, such as Neuregulin (NRG)-1Beta levels and incident risk of adverse cardiovascular outcomes in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that a sustained increase in NRG-1Beta, indicative of enhanced cardiac stress with exposure to chemotherapeutic agents, is predictive of an increased risk of cardiac dysfunction and heart failure.
- To study the single nucleotide polymorphism (SNP)/haplotype variation in pathways of interest, such as the Neuregulin/Epidermal Growth Factor (ErbB) signaling pathway, on incident risk of adverse cardiovascular outcomes. We hypothesize that there will be SNP/haplotypes variations that are associated with incident cardiovascular outcomes.
- To determine the longitudinal relationships between novel echocardiographic measures, such as strain and strain rate and incident cardiac dysfunction in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that early declines in strain and strain rate are predictive of an increased risk of future cardiac dysfunction and heart failure.
- To explore the changes in biomarkers such as NRG-1Beta levels and the relationships with novel echocardiographic measures of cardiac function.
- To create a biobank as a future resource for additional questions in novel biomarkers and genetics.
- To determine the long-term effects of cancer therapy cardiotoxicity by following patients yearly for 5 years after their exposure to cancer therapy, with the option to extend up to an additional 5 years.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Subgroup 2 | – | Diagnostic Test: Echocardiography, Other: Blood Collection, Other: Symptoms QuestionnaireSubgroup2 represents will undergo trastuzumab therapy only |
| Subgroup 1 | – | Diagnostic Test: Echocardiography, Other: Blood Collection, Other: Symptoms QuestionnaireSubgroup 1 are anthracycline only treated patients. |
| Subgroup 3 | – | Diagnostic Test: Echocardiography, Other: Blood Collection, Other: Symptoms QuestionnaireSubgroup 3 are patients that will undergo trastuzumab therapy with anthracyclines. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Subjects with breast cancer will enter the cohort prior to chemotherapy initiation and be evaluated at baseline and at regular intervals during the first approximately 15 months after chemotherapy is initiated. Patients will have study visits at 2 years, 3 years, 5, years, 7 years, 9 years, 11 years, 13 years, and 15 years following initiation of cancer therapy.
Key inclusion criteria (3 listed)
- Age 18 years or older
- HER-2 positive breast cancer designated to receive trastuzumab chemotherapy with or without prior exposure to anthracycline-based chemotherapy
- Non-HER-2 positive breast cancer designated to receive treatment with an anthracycline-containing regimen
Key exclusion criteria (2 listed)
- Other contraindications to trastuzumab or anthracycline chemotherapy.
- Vulnerable populations
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EchocardiographyPrior to chemotherapy, prior to and after anthracyclines, every 6 weeks during trastuzumab, and yearly for up to 10 years. | Diagnostic test | Subgroup 1, Subgroup 2, Subgroup 3 |
| Blood CollectionDrawn at first chemo treatment and periodically during treatment (exact schedule varies with clinically ordered treatment plan), then annually for up to 10 years. Blood is banked for future biomarker testing. | Other | Subgroup 1, Subgroup 2, Subgroup 3 |
| Symptoms QuestionnaireSurvey collected at first chemotherapy, periodically during therapy (exact schedule determined by clinically ordered treatment regimen), and annually for up to 10 years. | Other | Subgroup 1, Subgroup 2, Subgroup 3 |
Primary outcome
Cardiac dysfunction or signs or symptoms of heart failure
Time frame: 15 years
Cardiac dysfunction. as defined according to the Cardiac Review and Evaluation Committee (CREC) criteria as a decline in LVEF of 10% to less than 55% without signs or symptoms
1 secondary outcome
Change in quantitated Left Ventricular Ejection Fraction (LVEF)
Time frame: 15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Derived from this study: PubMed 42969899Wilcox NS, Xia C, Yang W, Ko K, Smith AM, Zhang L, Liu PP, Pei L, Baur JA, Cappola TP, Ky B. Early Increases in GDF-15 Are Associated With Declines in Cardiac Function With Breast Cancer Therapy. JACC Adv. 2026 Nov 2:103370. doi: 10.1016/j.jacadv.2026.103370. Online ahead of print.
- Derived from this study: PubMed 31959034Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan V, Domchek SM, DeMichele A, Shah P, Clark AS, Fox K, Matro J, Bradbury AR, Knollman H, Getz KD, Armenian SH, Januzzi JL, Tang WHW, Liu P, Ky B. Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction. J Am Heart Assoc. 2020 Jan 21;9(2):e014708. doi: 10.1161/JAHA.119.014708. Epub 2020 Jan 21.
- Derived from this study: PubMed 31542526Upshaw JN, Finkelman B, Hubbard RA, Smith AM, Narayan HK, Arndt L, Domchek S, DeMichele A, Fox K, Shah P, Clark A, Bradbury A, Matro J, Adusumalli S, Carver JR, Ky B. Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy. JACC Cardiovasc Imaging. 2020 Jan;13(1 Pt 2):198-210. doi: 10.1016/j.jcmg.2019.07.018. Epub 2019 Sep 18.
- Derived from this study: PubMed 30987448Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nunez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F, John Baksi A, O'Regan DP, Rosen SD, Prasad SK, Lara-Pezzi E, Provencio M, Lyon AR, Alonso-Pulpon L, Cook SA, DePalma SR, Barton PJR, Aplenc R, Seidman JG, Ky B, Ware JS, Seidman CE. Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy. Circulation. 2019 Jul 2;140(1):31-41. doi: 10.1161/CIRCULATIONAHA.118.037934. Epub 2019 Apr 16.
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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.
Bonnie Ky, MD principal investigator
Abramson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site 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 3 inclusion and 2 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: enrolling by invitation, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
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?
Cardiac dysfunction or signs or symptoms of heart failure (time frame: 15 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01173341, which also lists 4 linked publications.
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 9 Feb 2026.