Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

CYP3A5 Gene as a Risk Factor for Kidney Damage in Young Patients With Cancer Treated With Ifosfamide

Basic Trial Information

Objectives

Primary

1. To determine the CYP3A5 genotype in young patients with cancer who have received ifosfamide.
2. To document renal function and nephrotoxicity on one occasion between 1 month and 5 years after completion of ifosfamide treatment.
3. To determine the relationship between CYP3A5 genotype and ifosfamide nephrotoxicity.

Secondary

1. To compare the measured glomerular filtration rate (GFR) (using a radioisotope clearance method) with that calculated using the Cole (weight and creatinine) model.

Entry Criteria

Disease Characteristics:

• Received ifosfamide before the age of 21 as part of treatment for cancer including, but not limited to, any of the following:
  • Ewing sarcoma
  • Rhabdomyosarcoma
  • Non-rhabdomyosarcoma soft tissue sarcoma

• No renal infiltration by tumor at any stage of illness

• May have been treated on one of the following clinical trials:
  • Euro-Ewing-Intergroup-EE99
  • SIOP-MMT-95 
    • Patients who received CEV chemotherapy (carboplatin, epirubicin, and vincristine) on strategy 952 or 953 are not eligible
  • CCLG-EPSSG-NRSTS-2005
  • CCLG-EPSSG-RMS-2005

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from the acute non-renal toxicity of the last course of chemotherapy
• No other prior nephrotoxic chemotherapy (e.g., cisplatin, carboplatin, melphalan, or high-dose methotrexate)
• No prior radiotherapy to a field including the kidneys
• No prior removal of renal tissue
• No concurrent ifosfamide

Patient Characteristics:

• Clinically stable to undergo renal investigations
• No pre-existing renal impairment (glomerular or tubular) prior to treatment with ifosfamide
• No known nephrotoxicity for which nephrotoxic supportive treatment (aminoglycosides, amphotericin, acyclovir, cyclosporine, or tacrolimus) was a major contributory cause of renal damage

Expected Enrollment

Outcomes

CYP3A5 genotype
Renal function and nephrotoxicity
Relationship between CYP3A5 genotype and ifosfamide nephrotoxicity

Comparison of measured glomerular filtration rate (GFR) with the Cole model

Outline

This is a multicenter study.

Nephrotoxicity assessment is performed in patients who have not undergone prior assessment*.

 [Note: *Nephrotoxicity assessment is performed once between 1 month and 5 years after completion of ifosfamide chemotherapy.]

All patients will undergo a single blood sample collection. DNA will be extracted from this sample and genotyped for the known functional polymorphisms in CYP3A5. The technique of restriction fragment length polymorphism (RFLP) will be used to detect any single nucleotide polymorphisms in CYP3A5.

DNA may be obtained from stored tumor samples from patients for whom the results of renal investigations are available, but for whom blood is not available for CYP3A5 genotyping.

Trial Contact Information

Trial Lead Organizations

Children's Cancer and Leukaemia Group

Gareth Veal, Principal investigator		Ph: 44-191-246-4332

Ireland
	Dublin
	Our Lady's Hospital for Sick Children Crumlin
		Contact Person	Ph:  353-1-409-6659
United Kingdom
England
	Birmingham
	Birmingham Children's Hospital
		Martin English, MD	Ph:  44-121-333-8412
			Email: martin.english@bch.nhs.uk
	Bristol
	Bristol Royal Hospital for Children
		Contact Person	Ph:  44-117-342-0205
	Cambridge
	Addenbrooke's Hospital
		Amos Burke, MD	Ph:  44-1223-348-151
	Leeds
	Leeds Cancer Centre at St. James's University Hospital
		Adam Glaser, MD	Ph:  44-113-206-4984
			Email: adam.glaser@leedsth.nhs.uk
	Leicester
	Leicester Royal Infirmary
		Johann Visser, MD	Ph:  44-116-258-5309
			Email: johannes.visser@uhl-tr.nhs.uk
	Liverpool
	Royal Liverpool Children's Hospital, Alder Hey
		Heather McDowell, MD	Ph:  44-151-293-3679
	London
	Great Ormond Street Hospital for Children
		Gill Levitt, MD	Ph:  44-20-7405-9200 ext. 0073
	University College Hospital
		Maria Michelagnoli, MD	Ph:  44-20-7380-9064
			Email: maria.michelagnoli@uclh.nhs.uk
	Manchester
	Royal Manchester Children's Hospital
		Bernadette Brennan, MD	Ph:  44-161-922-2227
			Email: bernadette.brennan@cmmc.nhs.uk
	Newcastle-Upon-Tyne
	Sir James Spence Institute of Child Health at Royal Victoria Infirmary
		Juliet Hale, MD	Ph:  44-191-282-4101
			Email: j.p.hale@ncl.ac.uk
	Nottingham
	Queen's Medical Centre
		Martin Hewitt, MD, BSc, FRCP, FRCPCH	Ph:  44-115-924-9924 ext. 63394
			Email: martin.hewitt@nuh.nhs.uk
	Oxford
	Oxford Radcliffe Hospital
		Kate Wheeler, MD	Ph:  44-186-522-1066
	Sheffield
	Children's Hospital - Sheffield
		Mary Gerrard, MBChB, FRCP, FRCPCH	Ph:  44-114-271-7366
			Email: mary.gerrard@sch.nhs.uk
	Southampton
	Southampton General Hospital
		Janice Kohler, MD, FRCP	Ph:  44-23-8079-6942
	Sutton
	Royal Marsden - Surrey
		Mary Taj, MD	Ph:  44-20-8642-6011 ext. 3089
Northern Ireland
	Belfast
	Royal Belfast Hospital for Sick Children
		Anthony McCarthy, MD	Ph:  44-289-063-3631
			Email: anthonymcarthy@royalhospital.n.i.nhs.uk
Scotland
	Aberdeen
	Royal Aberdeen Children's Hospital
		Veronica Neefjes	Ph:  44-1224-550-217
	Edinburgh
	Royal Hospital for Sick Children
		W. Hamish Wallace, MD	Ph:  44-131-536-0426
	Glasgow
	Royal Hospital for Sick Children
		Milind Ronghe, MD	Ph:  44-141-201-9309
Wales
	Cardiff
	Childrens Hospital for Wales
		Heidi Traunecker, MD, PhD	Ph:  44-29-2074-2285
			Email: heidi.traunecker@cardiffandvale.wales.nhs.uk

Related Information

PDQ® clinical trial EURO-EWING-INTERGROUP-EE99
PDQ® clinical trial SIOP-MMT-95
PDQ® clinical trial CCLG-EPSSG-RMS-2005
PDQ® clinical trial CCLG-EPSSG-NRSTS-2005

Registry Information
Official Title		CYP3A5 Genotype as a Potential Risk Factor for the Development of Ifosamide Nephrotoxicity in Children
Trial Start Date		2007-07-01
Registered in ClinicalTrials.gov		NCT00514345
Date Submitted to PDQ		2007-07-16
Information Last Verified		2009-06-14

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