Anthracycline-induced CardiotoxicityPCS2NCT01805778
Preventing Cardiac Sequelae in Pediatric Cancer Survivors
An observational study of Anthracycline-induced Cardiotoxicity, run by The Hospital for Sick Children at 6 sites in 2 countries.
Trial summary
Cancer therapy can place childhood cancer survivors at increased risk for heart disease which can lead to significant illness or early death. Interventions that occur late in the evolution of treatment-related heart disease are usually ineffective at preventing its progression to death or heart transplant. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Anthracycline-induced Cardiotoxicity
- How many people
- 1,128 participants
- Where
- 6 sitesin 2 countries
- Study dates
- Dec 2012to Sep 2018
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patients will be recruited from pediatric oncology centres across Ontario, Canada (SickKids in Toronto, McMaster Children's Hospital in Hamilton, Children's Hospital of Eastern Ontario in Ottawa, and London Health Sciences Centre in London) as well as Princess Margaret Cancer Centre (Toronto) and Children's Hospital of Orange County (California, U.S.).
Who may be able to join
- Aged <18 years at time of cancer diagnosis
- Diagnosed with a new malignancy (patients with a history of a prior malignancy wlil be eligible if they have not received any anthracycline chemotherapy or chest radiation)
- Cancer treatment plan will require therapy with at least one dose of any anthracycline
- Planned to have all pre-anthracycline echocardiograms (ECHO) at the recruiting site
- Normal cardiac functioning prior to initiation of anthracycline therapy (LV EF > 55%)
- Patients who are uncooperative during the ECHO without sedation or anesthesia will be included in the study. However, these patients will only undergo clinically indicated echocardiograms, with no echocardiograms added for purely research purposes
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- Provision of signed informed consent by the patient and/or patient's legal guardian
- Aged < 18 years at time of cancer diagnosis
- Previously diagnosed with cancer and currently in remission
- Patients whose prior treatment plan included therapy with at least one dose of any anthracycline
- Patients who completed their final dose of anthracycline at least 3 years ago
- Routinely followed at the recruiting site approximately ever 12 months
Who cannot join
- Patients who were previously treated with anthracycline chemotherapy or radiation to the chest.
- Significant congenital heart defects, including patients with any other congenital cardiac abnormality, except those with a patent foramen ovale or a small ASD. Patients with familial cardiomyopathies (hypertrophic, dilated and restrictive) will be excluded.
- SURVIVOR COHORT:
- Prior allogeneic stem cell transplant
- Significant congenital heart defects, including patients with any other congenital cardiac abnormality, except those with a patent foramen ovale or a small ASD. Patients with familial cardiomyopathies (hypertrophic, dilated and restrictive) will be excluded.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Canada5 sites
McMaster Children's Hospital
Hamilton, Ontario
London Health Sciences Centre
London, Ontario
Children's Hospital of Eastern Ontario
Ottawa, Ontario
SickKids
Toronto, Ontario, M5G1XE
Princess Margaret Hospital
Toronto, Ontario, M5T2M9
United States1 site
Children's Hospital of Orange County
Orange, California, 92868
About this study
Official title: Novel Approaches to the Prediction, Diagnosis and Treatment of Cardiac Late Effects in Survivors of Childhood Cancer: A Multi-centre Observational Study
Cancer therapy can place childhood cancer survivors at increased risk for heart disease which can lead to significant illness or early death. Interventions that occur late in the evolution of treatment-related heart disease are usually ineffective at preventing its progression to death or heart transplant. Our team will work in several research cores to test new imaging and biomarker methods that will lead to earlier detection of heart disease before clinical symptoms develop or it become apparent on standard imaging tests. We will evaluate the importance of genetic differences between individuals in determining who is at greatest risk of developing heart disease as a result of exposure to cardiotoxic agents. We will combine this genetic information with the novel imaging and biomarker methods to predict which children are at particular risk. These vulnerable children can then be targeted by modifying their cancer therapy to reduce their exposure to cardiac toxins, or introducing medications that protect the heart from chemotherapy damage. This team brings together the expertise of clinicians and scientists in pediatric oncology, pediatric and adult cardiology, radiation oncology, genetics, and biostatistics. This is a cross-Canada initiative that will leverage the latest knowledge about cardiac toxicity and create a resource for ongoing research into this important cause of morbidity and mortality in childhood cancer survivors.
Read the detailed description
This is a multi-centre observational cohort study that will be conducted at The Hospital for Sick Children (Toronto), Princess Margaret Hospital (Toronto), McMaster Children's Hospital (Hamilton), London Health Sciences Centre (London), The Children's Hospital of Eastern Ontario (Ottawa) and The Children's Hospital of Orange County (Orange County, California).
The study will address the current limitations in prediction and early diagnosis of anthracycline-induced heart disease. This will be accomplished by the following 3 collaborative cores:
Core 1 (Genomics) will focus on determining which children are most susceptible to treatment-related cardiac toxicity by assessing genes in pathways related to anthracycline absorption, distribution, metabolism, and excretion, as well identifying genes in pathways known to be important in the cardiac response to injury.
Core 2 (Biomarkers) will explore whether existing and novel biomarkers allow for more accurate diagnosis of acute and late treatment-related cardiac toxicity. The core will use a human stem cell platform for discovery of novel biomarkers of anthracycline cardiac damage that will be evaluated in our clinical cohort.
Core 3 (Cardiac imaging) will focus on the evaluation of new echocardiographic and CMR techniques aimed at early identification of cardiac damage after anthracycline exposure.
It will investigate whether changes in cardiac function immediately after anthracycline administration predict which patients will develop progressive cardiac disease over time, and it will explore disease progression through the longitudinal evaluation of innovative echocardiographic parameters of remodeling and dysfunction in CCS exposed to anthracyclines.
- Conditions
- Anthracycline-induced Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Acute Cohort | Patients newly diagnosed with cancer who will be receiving anthracycline chemotherapy | |
| Survivor Cohort | Survivors of childhood cancer who are at least 3 years or more from their last dose of anthracycline therapy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Remodeling
The presence of one or more of the following:
- Cardiac Remodeling defined as Left Ventricular Posterior Wall Thickness (LVPWT) or Thickness to Dimension Ratio (TDR) z-score <-2.0 or a reduction in LVPWT or TDR z-score by at least 1 standard deviation compared to baseline; or
- Reduced left ventricular ejection fraction (LV EF) (<55%); or
- Symptomatic heart failure graded using New York Heart Association (NYHA) classification (or Ross heart failure class at least 2 in infants less than 2 years old)
Measured: one year after last dose of anthracycline therapy in Acute Cohort; anytime during 2 year follow up in Survivor Cohort
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2013 (estimated)
- Study startDec 2012
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Anthracycline-induced CardiotoxicityStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- 1,128 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Ontario Institute for Cancer Research, Pediatric Oncology Group of Ontario, C17 Council, Ottawa Heart Institute Research Corporation, Montreal Heart Institute, McMaster Children's Hospital, Children's Hospital of Eastern Ontario, London Health Sciences Centre, Children's Hospital of Orange County, Princess Margaret Hospital, Canada
- Responsible party
- Principal investigator, Paul Nathan, The Hospital for Sick Children
- Investigators
- Paul C Nathan, M.D., Principal investigator, The Hospital for Sick ChildrenMark Greenberg, M.D., Principal investigator, The Hospital for Sick ChildrenSeema Mital, M.D., Principal investigator, The Hospital for Sick ChildrenLuc Mertens, M.D., Principal investigator, The Hospital for Sick ChildrenPaul Kantor, M.D., Principal investigator, University of Alberta/Stollery Children's HospitalPeter Liu, M.D., Principal investigator, Ottawa Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01805778
- Sponsor's protocol ID
- 1000032746
- Acronym
- PCS2
- Status last verified
- Jul 2019
- First submitted
- 28 Feb 2013
- Last updated
- 8 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Chaix MA, Parmar N, Kinnear C, Lafreniere-Roula M, Akinrinade O, Yao R, Miron A, Lam E, Meng G, Christie A, Manickaraj AK, Marjerrison S, Dillenburg R, Bassal M, Lougheed J, Zelcer S, Rosenberg H, Hodgson D, Sender L, Kantor P, Manlhiot C, Ellis J, Mertens L, Nathan PC, Mital S. Machine Learning Identifies Clinical and Genetic Factors Associated With Anthracycline Cardiotoxicity in Pediatric Cancer Survivors. JACC CardioOncol. 2020 Dec 15;2(5):690-706. doi: 10.1016/j.jaccao.2020.11.004. eCollection 2020 Dec.
PubMed 34396283Skitch A, Mital S, Mertens L, Liu P, Kantor P, Grosse-Wortmann L, Manlhiot C, Greenberg M, Nathan PC. Novel approaches to the prediction, diagnosis and treatment of cardiac late effects in survivors of childhood cancer: a multi-centre observational study. BMC Cancer. 2017 Aug 3;17(1):519. doi: 10.1186/s12885-017-3505-0.
PubMed 28774277
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Approaches to the Prediction, Diagnosis and Treatment of Cardiac Late Effects in Survivors of Childhood Cancer: A Multi-centre Observational Study
- ClinicalTrials.gov ID
- NCT01805778
- Acronym / sponsor ID
- PCS2 / 1000032746
- Conditions
- Anthracycline-induced Cardiotoxicity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,128 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Ontario Institute for Cancer Research, Pediatric Oncology Group of Ontario, C17 Council, Ottawa Heart Institute Research Corporation, Montreal Heart Institute, McMaster Children's Hospital, Children's Hospital of Eastern Ontario, London Health Sciences Centre, Children's Hospital of Orange County, Princess Margaret Hospital, Canada
- Study start
- Dec 2012 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 6 Mar 2013 (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.
Cancer therapy can place childhood cancer survivors at increased risk for heart disease which can lead to significant illness or early death. Interventions that occur late in the evolution of treatment-related heart disease are usually ineffective at preventing its progression to death or heart transplant. Our team will work in several research cores to test new imaging and biomarker methods that will lead to earlier detection of heart disease before clinical symptoms develop or it become apparent on standard imaging tests. We will evaluate the importance of genetic differences between individuals in determining who is at greatest risk of developing heart disease as a result of exposure to cardiotoxic agents. We will combine this genetic information with the novel imaging and biomarker methods to predict which children are at particular risk. These vulnerable children can then be targeted by modifying their cancer therapy to reduce their exposure to cardiac toxins, or introducing medications that protect the heart from chemotherapy damage. This team brings together the expertise of clinicians and scientists in pediatric oncology, pediatric and adult cardiology, radiation oncology, genetics, and biostatistics. This is a cross-Canada initiative that will leverage the latest knowledge about cardiac toxicity and create a resource for ongoing research into this important cause of morbidity and mortality in childhood cancer survivors.
Detailed description
This is a multi-centre observational cohort study that will be conducted at The Hospital for Sick Children (Toronto), Princess Margaret Hospital (Toronto), McMaster Children's Hospital (Hamilton), London Health Sciences Centre (London), The Children's Hospital of Eastern Ontario (Ottawa) and The Children's Hospital of Orange County (Orange County, California).
The study will address the current limitations in prediction and early diagnosis of anthracycline-induced heart disease. This will be accomplished by the following 3 collaborative cores:
Core 1 (Genomics) will focus on determining which children are most susceptible to treatment-related cardiac toxicity by assessing genes in pathways related to anthracycline absorption, distribution, metabolism, and excretion, as well identifying genes in pathways known to be important in the cardiac response to injury.
Core 2 (Biomarkers) will explore whether existing and novel biomarkers allow for more accurate diagnosis of acute and late treatment-related cardiac toxicity. The core will use a human stem cell platform for discovery of novel biomarkers of anthracycline cardiac damage that will be evaluated in our clinical cohort.
Core 3 (Cardiac imaging) will focus on the evaluation of new echocardiographic and CMR techniques aimed at early identification of cardiac damage after anthracycline exposure.
It will investigate whether changes in cardiac function immediately after anthracycline administration predict which patients will develop progressive cardiac disease over time, and it will explore disease progression through the longitudinal evaluation of innovative echocardiographic parameters of remodeling and dysfunction in CCS exposed to anthracyclines.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acute Cohort | – | –Patients newly diagnosed with cancer who will be receiving anthracycline chemotherapy |
| Survivor Cohort | – | –Survivors of childhood cancer who are at least 3 years or more from their last dose of anthracycline therapy. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patients will be recruited from pediatric oncology centres across Ontario, Canada (SickKids in Toronto, McMaster Children's Hospital in Hamilton, Children's Hospital of Eastern Ontario in Ottawa, and London Health Sciences Centre in London) as well as Princess Margaret Cancer Centre (Toronto) and Children's Hospital of Orange County (California, U.S.).
Key inclusion criteria (12 listed)
- Aged <18 years at time of cancer diagnosis
- Diagnosed with a new malignancy (patients with a history of a prior malignancy wlil be eligible if they have not received any anthracycline chemotherapy or chest radiation)
- Cancer treatment plan will require therapy with at least one dose of any anthracycline
- Planned to have all pre-anthracycline echocardiograms (ECHO) at the recruiting site
- Normal cardiac functioning prior to initiation of anthracycline therapy (LV EF > 55%)
Key exclusion criteria (5 listed)
- Patients who were previously treated with anthracycline chemotherapy or radiation to the chest.
- Significant congenital heart defects, including patients with any other congenital cardiac abnormality, except those with a patent foramen ovale or a small ASD. Patients with familial cardiomyopathies (hypertrophic, dilated and restrictive) will be excluded.
- Prior allogeneic stem cell transplant
- Significant congenital heart defects, including patients with any other congenital cardiac abnormality, except those with a patent foramen ovale or a small ASD. Patients with familial cardiomyopathies (hypertrophic, dilated and restrictive) will be excluded.
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
Cardiac Remodeling
Time frame: one year after last dose of anthracycline therapy in Acute Cohort; anytime during 2 year follow up in Survivor Cohort
The presence of one or more of the following: 1. Cardiac Remodeling defined as Left Ventricular Posterior Wall Thickness (LVPWT) or Thickness to Dimension Ratio (TDR) z-score <-2.0 or a reduction in LVPWT or TDR z-score by at least 1 standard deviation compared to baseline; or 2. Reduced left ventricular ejection fraction (LV EF) (<55%); or 3. Symptomatic heart failure graded using New York Heart Association (NYHA) classification (or Ross heart failure class at least 2 in infants less than 2 years old)
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 8 Jul 2019.
- Derived from this study: PubMed 34396283Chaix MA, Parmar N, Kinnear C, Lafreniere-Roula M, Akinrinade O, Yao R, Miron A, Lam E, Meng G, Christie A, Manickaraj AK, Marjerrison S, Dillenburg R, Bassal M, Lougheed J, Zelcer S, Rosenberg H, Hodgson D, Sender L, Kantor P, Manlhiot C, Ellis J, Mertens L, Nathan PC, Mital S. Machine Learning Identifies Clinical and Genetic Factors Associated With Anthracycline Cardiotoxicity in Pediatric Cancer Survivors. JACC CardioOncol. 2020 Dec 15;2(5):690-706. doi: 10.1016/j.jaccao.2020.11.004. eCollection 2020 Dec.
- Derived from this study: PubMed 28774277Skitch A, Mital S, Mertens L, Liu P, Kantor P, Grosse-Wortmann L, Manlhiot C, Greenberg M, Nathan PC. Novel approaches to the prediction, diagnosis and treatment of cardiac late effects in survivors of childhood cancer: a multi-centre observational study. BMC Cancer. 2017 Aug 3;17(1):519. doi: 10.1186/s12885-017-3505-0.
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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.
Paul C Nathan, M.D. principal investigator
The Hospital for Sick Children
Mark Greenberg, M.D. principal investigator
The Hospital for Sick Children
Seema Mital, M.D. principal investigator
The Hospital for Sick Children
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anthracycline-induced Cardiotoxicity, run by The Hospital for Sick Children at 6 sites in 2 countries.
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 12 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 8 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada, 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?
Cardiac Remodeling (time frame: one year after last dose of anthracycline therapy in Acute Cohort; anytime during 2 year follow up in Survivor Cohort). 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 NCT01805778, which also lists 2 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 8 Jul 2019.