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CYP3A5 Gene as a Risk Factor for Kidney Damage in Young Patients With Cancer Treated With Ifosfamide
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), June 2009
First Received: August 8, 2007   Last Updated: July 2, 2009   History of Changes
Sponsor: Children's Cancer and Leukaemia Group
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00514345
  Purpose

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

Study Type: Observational
Official Title: CYP3A5 Genotype as a Potential Risk Factor for the Development of Ifosamide Nephrotoxicity in Children

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • CYP3A5 genotype [ Designated as safety issue: No ]
  • Renal function and nephrotoxicity [ Designated as safety issue: Yes ]
  • Relationship between CYP3A5 genotype and ifosfamide nephrotoxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Comparison of measured glomerular filtration rate (GFR) with the Cole model [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: July 2007
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.

  Eligibility

Ages Eligible for Study:   up to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00514345

Locations
Ireland
Our Lady's Hospital for Sick Children Crumlin Recruiting
Dublin, Ireland, 12
Contact: Contact Person     353-1-409-6659        
United Kingdom, England
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Amos Burke, MD     44-1223-348-151        
Birmingham Children's Hospital Recruiting
Birmingham, England, United Kingdom, B4 6NH
Contact: Martin W. English, MD     44-121-333-8412     martin.english@bch.nhs.uk    
Bristol Royal Hospital for Children Recruiting
Bristol, England, United Kingdom, BS2 8BJ
Contact: Contact Person     44-117-342-0205        
Children's Hospital - Sheffield Recruiting
Sheffield, England, United Kingdom, S10 2TH
Contact: Mary P. Gerrard, MBChB, FRCP, FRCPCH     44-114-271-7366     mary.gerrard@sch.nhs.uk    
Queen's Medical Centre Recruiting
Nottingham, England, United Kingdom, NG7 2UH
Contact: Martin Hewitt, MD, BSc, FRCP, FRCPCH     44-115-924-9924 ext. 63394     martin.hewitt@nuh.nhs.uk    
Leeds Cancer Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS9 7TF
Contact: Adam Glaser, MD     44-113-206-4984     adam.glaser@leedsth.nhs.uk    
Leicester Royal Infirmary Recruiting
Leicester, England, United Kingdom, LE1 5WW
Contact: Johann Visser, MD     44-116-258-5309     johannes.visser@uhl-tr.nhs.uk    
Oxford Radcliffe Hospital Recruiting
Oxford, England, United Kingdom, 0X3 9DU
Contact: Kate Wheeler, MD     44-186-522-1066        
Great Ormond Street Hospital for Children Recruiting
London, England, United Kingdom, WC1N 3JH
Contact: Gill Levitt, MD     44-20-7405-9200 ext. 0073        
Royal Liverpool Children's Hospital, Alder Hey Recruiting
Liverpool, England, United Kingdom, L12 2AP
Contact: Heather P. McDowell, MD     44-151-293-3679        
Royal Manchester Children's Hospital Recruiting
Manchester, England, United Kingdom, M27 4HA
Contact: Bernadette Brennan, MD     44-161-922-2227     bernadette.brennan@cmmc.nhs.uk    
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Mary Taj, MD     44-20-8642-6011 ext. 3089        
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     j.p.hale@ncl.ac.uk    
Southampton General Hospital Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Janice A. Kohler, MD, FRCP     44-23-8079-6942        
University College Hospital Recruiting
London, England, United Kingdom, NW1 2PCE
Contact: Maria Michelagnoli, MD     44-20-7380-9064     maria.michelagnoli@uclh.nhs.uk    
United Kingdom, Northern Ireland
Royal Belfast Hospital for Sick Children Recruiting
Belfast, Northern Ireland, United Kingdom, BT12 6BE
Contact: Anthony McCarthy, MD     44-289-063-3631     anthonymcarthy@royalhospital.n.i.nhs.uk    
United Kingdom, Scotland
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
Glasgow, Scotland, United Kingdom, G3 8SJ
Contact: Milind D. Ronghe, MD     44-141-201-9309        
Royal Hospital for Sick Children Recruiting
Edinburgh, Scotland, United Kingdom, EH9 1LF
Contact: W. Hamish Wallace, MD     44-131-536-0426        
United Kingdom, Wales
Childrens Hospital for Wales Recruiting
Cardiff, Wales, United Kingdom, CF14 4XW
Contact: Heidi Traunecker, MD, PhD     44-29-2074-2285     heidi.traunecker@cardiffandvale.wales.nhs.uk    
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Investigators
Principal Investigator: Gareth Veal University of Newcastle Upon-Tyne
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000560128, CCLG-PK-2007-02, EU-20743
Study First Received: August 8, 2007
Last Updated: July 2, 2009
ClinicalTrials.gov Identifier: NCT00514345     History of Changes
Health Authority: Unspecified

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
Neuroectodermal Tumors
Neoplasms
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Sarcoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 08, 2010