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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chemotherapeutic Agent Toxicity, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Genetic: gene expression analysis
* Genetic: polymorphism analysis
* Procedure: management of therapy complications


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: gene expression analysis|nan|
|Genetic: polymorphism analysis|nan|
|Procedure: management of therapy complications|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CYP3A5 genotype |  |  | 
| Renal function and nephrotoxicity |  |  | 
| Relationship between CYP3A5 genotype and ifosfamide nephrotoxicity |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of measured glomerular filtration rate (GFR) with the Cole model |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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