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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00514345
Recruitment Status : Unknown
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
First Posted : August 9, 2007
Last Update Posted : August 12, 2013
Information provided by:
National Cancer Institute (NCI)

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
Chemotherapeutic Agent Toxicity Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific Genetic: gene expression analysis Genetic: polymorphism analysis Procedure: management of therapy complications

Detailed Description:



  • 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.


  • 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 Type : Observational
Estimated Enrollment : 300 participants
Official Title: CYP3A5 Genotype as a Potential Risk Factor for the Development of Ifosamide Nephrotoxicity in Children
Study Start Date : July 2007

Primary Outcome Measures :
  1. CYP3A5 genotype
  2. Renal function and nephrotoxicity
  3. Relationship between CYP3A5 genotype and ifosfamide nephrotoxicity

Secondary Outcome Measures :
  1. Comparison of measured glomerular filtration rate (GFR) with the Cole model

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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-RMS-2005


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00514345

Our Lady's Hospital for Sick Children Crumlin Recruiting
Dublin, Ireland, 12
Contact: Contact Person    353-1-409-6659      
United Kingdom
Birmingham Children's Hospital Recruiting
Birmingham, England, United Kingdom, B4 6NH
Contact: Martin W. English, MD    44-121-333-8412   
Bristol Royal Hospital for Children Recruiting
Bristol, England, United Kingdom, BS2 8BJ
Contact: Contact Person    44-117-342-0205      
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Amos Burke, MD    44-1223-348-151      
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Adam Glaser, MD    44-113-206-4984   
Leicester Royal Infirmary Recruiting
Leicester, England, United Kingdom, LE1 5WW
Contact: Johann Visser, MD    44-116-258-5309   
Royal Liverpool Children's Hospital, Alder Hey Recruiting
Liverpool, England, United Kingdom, L12 2AP
Contact: Heather P. McDowell, MD    44-151-293-3679      
University College Hospital Recruiting
London, England, United Kingdom, NW1 2PCE
Contact: Maria Michelagnoli, MD    44-20-7380-9064   
Great Ormond Street Hospital for Children Recruiting
London, England, United Kingdom, WC1N 3JH
Contact: Gill Levitt, MD    44-20-7405-9200 ext. 0073      
Royal Manchester Children's Hospital Recruiting
Manchester, England, United Kingdom, M27 4HA
Contact: Bernadette Brennan, MD    44-161-922-2227   
Sir James Spence Institute of Child Health at Royal Victoria Infirmary Recruiting
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Contact: Juliet Hale, MD    44-191-282-4101   
Queen's Medical Centre Recruiting
Nottingham, England, United Kingdom, NG7 2UH
Contact: Martin Hewitt, MD, BSc, FRCP, FRCPCH    44-115-924-9924 ext. 63394   
Oxford Radcliffe Hospital Recruiting
Oxford, England, United Kingdom, 0X3 9DU
Contact: Kate Wheeler, MD    44-186-522-1066      
Children's Hospital - Sheffield Recruiting
Sheffield, England, United Kingdom, S10 2TH
Contact: Mary P. Gerrard, MBChB, FRCP, FRCPCH    44-114-271-7366   
Southampton General Hospital Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Janice A. Kohler, MD, FRCP    44-23-8079-6942      
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Mary Taj, MD    44-20-8642-6011 ext. 3089      
Royal Belfast Hospital for Sick Children Recruiting
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Contact: Anthony McCarthy, MD    44-289-063-3631   
Royal Aberdeen Children's Hospital Recruiting
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Contact: Veronica Neefjes    44-1224-550-217      
Royal Hospital for Sick Children Recruiting
Edinburgh, Scotland, United Kingdom, EH9 1LF
Contact: W. Hamish Wallace, MD    44-131-536-0426      
Royal Hospital for Sick Children Recruiting
Glasgow, Scotland, United Kingdom, G3 8SJ
Contact: Milind D. Ronghe, MD    44-141-201-9309      
Childrens Hospital for Wales Recruiting
Cardiff, Wales, United Kingdom, CF14 4XW
Contact: Heidi Traunecker, MD, PhD    44-29-2074-2285   
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Principal Investigator: Gareth Veal University of Newcastle Upon-Tyne Identifier: NCT00514345     History of Changes
Other Study ID Numbers: CCLG-PK-2007-02
CDR0000560128 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: August 9, 2007    Key Record Dates
Last Update Posted: August 12, 2013
Last Verified: June 2009

Keywords provided by National Cancer Institute (NCI):
chemotherapeutic agent toxicity
localized Ewing sarcoma/peripheral primitive neuroectodermal tumor
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
nonmetastatic childhood soft tissue sarcoma
unspecified childhood solid tumor, protocol specific
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma
previously treated childhood rhabdomyosarcoma
recurrent childhood rhabdomyosarcoma

Additional relevant MeSH terms:
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type