Preventing Cardiac Sequelae in Pediatric Cancer Survivors

NCT01805778 | Completed

• 1 other identifier: 1000032746
• Study Type: observational
• Target: 1,128
• Locations: 2 countries
• Sites: 6

Brief 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. 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.

Conditions

Anthracycline-induced Cardiotoxicity

Outcome Measures

Primary Outcomes (1)

• Cardiac Remodeling

  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)

  one year after last dose of anthracycline therapy in Acute Cohort; anytime during 2 year follow up in Survivor Cohort

Study Arms (2)

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.

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

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.).

You may qualify if:

• 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
• Provision of signed informed consent by the patient and/or patient's legal guardian

You may not qualify if:

• 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:
• 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
• 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.

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Ontario Institute for Cancer Research: collaborator
• Pediatric Oncology Group of Ontario: collaborator
• C17 Council: collaborator
• Ottawa Heart Institute Research Corporation: collaborator
• Montreal Heart Institute: collaborator
• McMaster Children's Hospital: collaborator
• Children's Hospital of Eastern Ontario: collaborator
• London Health Sciences Centre: collaborator
• Children's Hospital of Orange County: collaborator
• Princess Margaret Hospital, Canada: collaborator

Study Sites (6)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

McMaster Children's Hospital

Hamilton, Ontario, Canada

Location

London Health Sciences Centre

London, Ontario, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Location

SickKids

Toronto, Ontario, M5G1XE, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5T2M9, Canada

Location

Related Publications (2)

• 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.

  PMID: 34396283 DERIVED

• Skitch 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.

  PMID: 28774277 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

The study will retain plasma for biomarker and genomic analysis. The study will also retain saliva for those patient who are unable or unwilling to provide a blood specimen for genomic analysis.

Study Officials

• Paul C Nathan, M.D.

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Mark Greenberg, M.D.

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Seema Mital, M.D.

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Luc Mertens, M.D.

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Paul Kantor, M.D.

  University of Alberta/Stollery Children's Hospital

  PRINCIPAL INVESTIGATOR

• Peter Liu, M.D.

  Ottawa Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director- Aftercare Program, Staff Oncologist

Study Record Dates

• First Submitted: February 28, 2013
• First Posted: March 6, 2013
• Study Start: December 1, 2012
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: July 8, 2019

Record last verified: 2019-07

Locations

CA (5); US (1)