Early Detection of Cardiac Toxicity in Childhood Cancer Survivors

Heart Failure Clinical Trial

Official title:

Early Detection of Cardiac Toxicity in Childhood Cancer Survivors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03038997
• Other study ID #: 5405
• Status: Terminated
• Start date: November 2014
• Est. completion date: March 11, 2018

Study information

• Verified date: November 2018
• Source: Children's Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To evaluate cardiac MRI and/or serum biomarkers for detecting cardiac cardiac toxicity in children who received anthracycline based chemotherapy (ABC).

Description:

Cardiac toxicity is a significant potential complication for patients receiving anthracycline chemotherapy. Cells in the cardiovascular system have limited regenerative capability, making them susceptible to long term adverse effects from these chemotherapeutic agents. The ability to detect subclinical changes in cardiac function will allow clinicians to use proven treatments to prevent further progression in this vulnerable population. The current standard testing uses echocardiography, which is not as sensitive as cardiac MRI or serum biomarkers.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: March 11, 2018
• Est. primary completion date: March 11, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 25 Years

Eligibility

Inclusion Criteria:

• Subjects that have received anthracycline based chemotherapy

• Age: 8 years old - 25 years old

• Subjects that do not require sedation for cardiac MRI.

• Subjects must have completed treatment in the last 10 years

Exclusion Criteria:

• Patients with significant congenital heart defects

• Patients with renal injury or renal failure, defined as an estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2 body surface area), as previously calculated)

• Patients that require sedation for a cardiac MRI

• Subjects that are pregnant or lactating

• Patients with contraindications to a cardiac MRI:

• Cardiac pacemaker or implantable defibrillator

• Cerebral aneurysm clip

• Neural stimulator

• Metallic ocular foreign body

• Any implanted device (i.e. insulin pump, drug infusion device)

• Claustrophobia

• Metal shrapnel or bullet

• Investigator assessment of inability to comply with protocol

• Unable/unwilling to lie still throughout the research procedure

• Persons with cognitive impairment

Related Conditions & MeSH terms

• Cardiotoxicity
• Heart Failure

Locations

Country	Name	City	State
United States	Children's National Health System	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Niti Dham

Country where clinical trial is conducted

United States, 

References & Publications (27)

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Florian A, Ludwig A, Rösch S, Yildiz H, Sechtem U, Yilmaz A. Myocardial fibrosis imaging based on T1-mapping and extracellular volume fraction (ECV) measurement in muscular dystrophy patients: diagnostic value compared with conventional late gadolinium enhancement (LGE) imaging. Eur Heart J Cardiovasc Imaging. 2014 Sep;15(9):1004-12. doi: 10.1093/ehjci/jeu050. Epub 2014 Mar 30. — View Citation

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Kremer LC, van Dalen EC, Offringa M, Voûte PA. Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review. Ann Oncol. 2002 Apr;13(4):503-12. Review. — View Citation

Kremer LC, van der Pal HJ, Offringa M, van Dalen EC, Voûte PA. Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol. 2002 Jun;13(6):819-29. Review. — View Citation

Ky B, Putt M, Sawaya H, French B, Januzzi JL Jr, Sebag IA, Plana JC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2014 Mar 4;63(8):809-16. doi: 10.1016/j.jacc.2013.10.061. Epub 2013 Nov 27. Erratum in: J Am Coll Cardiol. 2016 Mar 22;67(11):1385. — View Citation

Lai WW, Geva T, Shirali GS, Frommelt PC, Humes RA, Brook MM, Pignatelli RH, Rychik J; Task Force of the Pediatric Council of the American Society of Echocardiography; Pediatric Council of the American Society of Echocardiography. Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography. J Am Soc Echocardiogr. 2006 Dec;19(12):1413-30. — View Citation

Lipshultz SE, Adams MJ, Colan SD, Constine LS, Herman EH, Hsu DT, Hudson MM, Kremer LC, Landy DC, Miller TL, Oeffinger KC, Rosenthal DN, Sable CA, Sallan SE, Singh GK, Steinberger J, Cochran TR, Wilkinson JD; American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Basic Cardiovascular Sciences, Council on Cardiovascular and Stroke Nursing, Council on Cardiovascular Radiolo. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation. 2013 Oct 22;128(17):1927-95. doi: 10.1161/CIR.0b013e3182a88099. Epub 2013 Sep 30. Erratum in: Circulation. 2013 Nov 5;128(19):e394. — View Citation

Lunning MA, Kutty S, Rome ET, Li L, Padiyath A, Loberiza F, Bociek RG, Bierman PJ, Vose JM, Armitage JO, Porter TR. Cardiac magnetic resonance imaging for the assessment of the myocardium after doxorubicin-based chemotherapy. Am J Clin Oncol. 2015 Aug;38(4):377-81. doi: 10.1097/COC.0b013e31829e19be. — View Citation

Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ. Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J. 2005 Aug;26(15):1461-74. Epub 2005 Apr 14. Review. — View Citation

Mavinkurve-Groothuis AM, Marcus KA, Pourier M, Loonen J, Feuth T, Hoogerbrugge PM, de Korte CL, Kapusta L. Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study. Eur Heart J Cardiovasc Imaging. 2013 Jun;14(6):562-9. doi: 10.1093/ehjci/jes217. Epub 2012 Oct 29. — View Citation

Menon SC, Etheridge SP, Liesemer KN, Williams RV, Bardsley T, Heywood MC, Puchalski MD. Predictive value of myocardial delayed enhancement in Duchenne muscular dystrophy. Pediatr Cardiol. 2014 Oct;35(7):1279-85. doi: 10.1007/s00246-014-0929-z. Epub 2014 May 15. — View Citation

Oberholzer K, Kunz RP, Dittrich M, Thelen M. [Anthracycline-induced cardiotoxicity: cardiac MRI after treatment for childhood cancer]. Rofo. 2004 Sep;176(9):1245-50. German. — View Citation

Pirat B, McCulloch ML, Zoghbi WA. Evaluation of global and regional right ventricular systolic function in patients with pulmonary hypertension using a novel speckle tracking method. Am J Cardiol. 2006 Sep 1;98(5):699-704. Epub 2006 Jul 17. — View Citation

Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012 Sep 1;5(5):596-603. Epub 2012 Jun 28. — View Citation

Schwartz RG, Jain D, Storozynsky E. Traditional and novel methods to assess and prevent chemotherapy-related cardiac dysfunction noninvasively. J Nucl Cardiol. 2013 Jun;20(3):443-64. doi: 10.1007/s12350-013-9707-1. Review. — View Citation

Shankar SM, Marina N, Hudson MM, Hodgson DC, Adams MJ, Landier W, Bhatia S, Meeske K, Chen MH, Kinahan KE, Steinberger J, Rosenthal D; Cardiovascular Disease Task Force of the Children's Oncology Group. Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children's Oncology Group. Pediatrics. 2008 Feb;121(2):e387-96. doi: 10.1542/peds.2007-0575. Epub 2008 Jan 10. Review. — View Citation

Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schwartz RG, Shaffer EM, Sandor G, Benson L, Williams R. Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group. Pediatrics. 1992 May;89(5 Pt 1):942-9. — View Citation

Ugander M, Oki AJ, Hsu LY, Kellman P, Greiser A, Aletras AH, Sibley CT, Chen MY, Bandettini WP, Arai AE. Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. Eur Heart J. 2012 May;33(10):1268-78. doi: 10.1093/eurheartj/ehr481. Epub 2012 Jan 24. — View Citation

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Weidemann F, Jamal F, Sutherland GR, Claus P, Kowalski M, Hatle L, De Scheerder I, Bijnens B, Rademakers FE. Myocardial function defined by strain rate and strain during alterations in inotropic states and heart rate. Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H792-9. — View Citation

Yildirim A, Tunaoglu FS, Kambur K, Pinarli FG. The utility of NT-proBNP and various echocardiographic methods in the determination of doxorubicin induced subclinical late cardiotoxicity. Kardiol Pol. 2013;71(1):40-6. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Echocardiogram marker measurements pre ABC chemo and post ABC	•Measure echocardiogram markers on pre anthracycline based chemotherapy (ABC) and post ABC echocardiograms, using standard echocardiogram measurements and speckle tracking.	At the end of each cardiac MRI exam through study completion, up to 5 years
Secondary	Detection of cardiac toxicity on MRI and echocardiogram	•Measure sensitivity of detecting cardiac toxicity between standard echocardiogram, speckle tracking on echo, and MRI	At the end of each cardiac MRI exam through study completion, up to 5 years
Secondary	Serum biomarkers correlation	•Correlate measurement of serum biomarkers with prevalence of cardiac changes measured on echocardiograms and MRI imaging.	At the end of the study, up to 10 years