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

Condition(s) targeted: Cancer-Related Problem/Condition; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Intervention: gene expression analysis (Procedure); management of therapy complications (Procedure); polymorphism analysis (Procedure)

Phase: N/A

Status: Recruiting

Sponsored by: Children's Cancer and Leukaemia Group

Official(s) and/or principal investigator(s):
Gareth Veal, Principal Investigator, Affiliation: University of Newcastle Upon-Tyne

RATIONALE: Studying the genes expressed in samples of blood from young patients with cancer treated with ifosfamide may help doctors identify risk factors for kidney damage.

PURPOSE: This clinical trial is looking at the CYP3A5 gene to see if having the gene may be a risk factor for kidney damage in young patients with cancer treated with ifosfamide.

Official title: CYP3A5 Genotype as a Potential Risk Factor for the Development of Ifosamide Nephrotoxicity in Children

Study design: N/A

Primary outcome:

CYP3A5 genotype

Renal function and nephrotoxicity

Relationship between CYP3A5 genotype and ifosfamide nephrotoxicity

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

Detailed description: OBJECTIVES:

Primary

- To determine the CYP3A5 genotype in young patients with cancer who have received

ifosfamide.

- To document renal function and nephrotoxicity on one occasion between 1 month and 5

years after completion of ifosfamide treatment.

- To determine the relationship between CYP3A5 genotype and ifosfamide nephrotoxicity.

Secondary

- To compare the measured glomerular filtration rate (GFR) (using a radioisotope clearance

method) with that calculated using the Cole (weight and creatinine) 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.

Minimum age: N/A. Maximum age: 20 Years. Gender(s): Both.

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

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

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

Our Lady's Hospital for Sick Children Crumlin, Dublin 12, Ireland; Recruiting
Contact Person, Phone: 353-1-409-6659

Addenbrooke's Hospital, Cambridge, England CB2 2QQ, United Kingdom; Recruiting
Amos Burke, MD, Phone: 44-1223-348-151

Birmingham Children's Hospital, Birmingham, England B4 6NH, United Kingdom; Recruiting
Martin W. English, MD, Phone: 44-121-333-8412, Email: martin.english@bch.nhs.uk

Bristol Royal Hospital for Children, Bristol, England BS2 8BJ, United Kingdom; Recruiting
Contact Person, Phone: 44-117-342-0205

Children's Hospital - Sheffield, Sheffield, England S10 2TH, United Kingdom; Recruiting
Mary P. Gerrard, BSc, MBChB, FRCP, FRCPCH, Phone: 44-114-271-7366, Email: mary.gerrard@sch.nhs.uk

Great Ormond Street Hospital for Children, London, England WC1N 3JH, United Kingdom; Recruiting
Gill Levitt, MD, Phone: 44-20-7405-9200 ext. 0073

Leeds Cancer Centre at St. James's University Hospital, Leeds, England LS9 7TF, United Kingdom; Recruiting
Adam Glaser, MD, Phone: 44-113-206-4984, Email: adam.glaser@leedsth.nhs.uk

Leicester Royal Infirmary, Leicester, England LE1 5WW, United Kingdom; Recruiting
Johann Visser, MD, Phone: 44-116-258-5309, Email: johannes.visser@uhl-tr.nhs.uk

Oxford Radcliffe Hospital, Oxford, England 0X3 9DU, United Kingdom; Recruiting
Kate Wheeler, MD, Phone: 44-186-522-1066

Queen's Medical Centre, Nottingham, England NG7 2UH, United Kingdom; Recruiting
Martin Hewitt, MD, BSc, FRCP, FRCPCH, Phone: 44-115-924-9924 ext. 63394, Email: martin.hewitt@nuh.nhs.uk

Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England L12 2AP, United Kingdom; Recruiting
Heather P. McDowell, MD, Phone: 44-151-293-3679

Royal Manchester Children's Hospital, Manchester, England M27 4HA, United Kingdom; Recruiting
Bernadette Brennan, MD, Phone: 44-161-922-2227, Email: bernadette.brennan@cmmc.nhs.uk

Royal Marsden - Surrey, Sutton, England SM2 5PT, United Kingdom; Recruiting
Mary Taj, MD, Phone: 44-20-8642-6011 ext. 3089

Sir James Spence Institute of Child Health, Newcastle-Upon-Tyne, England NE1 4LP, United Kingdom; Recruiting
Juliet Hale, MD, Phone: 44-191-282-4101, Email: j.p.hale@ncl.ac.uk

Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom; Recruiting
Janice A. Kohler, MD, FRCP, Phone: 44-23-8079-6942

University College Hospital, London, England NW1 2PCE, United Kingdom; Recruiting
Maria Michelagnoli, MD, Phone: 44-20-7380-9064, Email: maria.michelagnoli@uclh.nhs.uk

Royal Belfast Hospital for Sick Children, Belfast, Northern Ireland BT12 6BE, United Kingdom; Recruiting
Anthony McCarthy, MD, Phone: 44-289-063-3631, Email: anthonymcarthy@royalhospital.n.i.nhs.uk

Royal Aberdeen Children's Hospital, Aberdeen, Scotland AB25 2ZG, United Kingdom; Recruiting
Veronica Neefjes, Phone: 44-1224-550-217

Royal Hospital for Sick Children, Glasgow, Scotland G3 8SJ, United Kingdom; Recruiting
Milind D. Ronghe, MD, Phone: 44-141-201-9309

Royal Hospital for Sick Children, Edinburgh, Scotland EH9 1LF, United Kingdom; Recruiting
W. Hamish Wallace, MD, Phone: 44-131-536-0426

Childrens Hospital for Wales, Cardiff, Wales CF14 4XW, United Kingdom; Recruiting
Heidi Traunecker, MD, PhD, Phone: 44-29-2074-2285, Email: heidi.traunecker@cardiffandvale.wales.nhs.uk

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: July 2007
Last updated: October 18, 2008