Clinical trial NCT00514345: CYP3A5 Gene as 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 type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chemotherapeutic Agent Toxicity
Sarcoma
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-08-09
Enrollment: 300
Sex: ALL
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no

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.

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 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

Primary outcomes:
measure: CYP3A5 genotype
measure: Renal function and nephrotoxicity
measure: Relationship between CYP3A5 genotype and ifosfamide nephrotoxicity
Secondary outcomes:
measure: Comparison of measured glomerular filtration rate (GFR) with the Cole model
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children Crumlin
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital, Alder Hey
state: England
city: London
country: United Kingdom
facility: University College Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: England
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health at Royal Victoria Infirmary
state: England
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Children's Hospital - Sheffield
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Cardiff
country: United Kingdom
facility: Childrens Hospital for Wales
state: Wales
Study officials:
affiliation: University of Newcastle Upon-Tyne
name: Gareth Veal
role: PRINCIPAL_INVESTIGATOR
References: