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

Sponsor

Children's Cancer and Leukaemia Group (Other)

Overall Status

Unknown status

CT.gov ID

NCT00514345

Collaborator

(none)

300

Enrollment

Locations

14.3

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapeutic Agent Toxicity Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific	Genetic: gene expression analysis Genetic: polymorphism analysis Procedure: management of therapy complications

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Official Title:

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

Study Start Date :

Jul 1, 2007

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Our Lady's Hospital for Sick Children Crumlin	Dublin		Ireland	12
2	Birmingham Children's Hospital	Birmingham	England	United Kingdom	B4 6NH
3	Bristol Royal Hospital for Children	Bristol	England	United Kingdom	BS2 8BJ
4	Addenbrooke's Hospital	Cambridge	England	United Kingdom	CB2 2QQ
5	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
6	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE1 5WW
7	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England	United Kingdom	L12 2AP
8	University College Hospital	London	England	United Kingdom	NW1 2PCE
9	Great Ormond Street Hospital for Children	London	England	United Kingdom	WC1N 3JH
10	Royal Manchester Children's Hospital	Manchester	England	United Kingdom	M27 4HA
11	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England	United Kingdom	NE1 4LP
12	Queen's Medical Centre	Nottingham	England	United Kingdom	NG7 2UH
13	Oxford Radcliffe Hospital	Oxford	England	United Kingdom	0X3 9DU
14	Children's Hospital - Sheffield	Sheffield	England	United Kingdom	S10 2TH
15	Southampton General Hospital	Southampton	England	United Kingdom	SO16 6YD
16	Royal Marsden - Surrey	Sutton	England	United Kingdom	SM2 5PT
17	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland	United Kingdom	BT12 6BE
18	Royal Aberdeen Children's Hospital	Aberdeen	Scotland	United Kingdom	AB25 2ZG
19	Royal Hospital for Sick Children	Edinburgh	Scotland	United Kingdom	EH9 1LF
20	Royal Hospital for Sick Children	Glasgow	Scotland	United Kingdom	G3 8SJ
21	Childrens Hospital for Wales	Cardiff	Wales	United Kingdom	CF14 4XW