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

Children's Cancer and Leukaemia Group300 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

300

Conditions

Chemotherapeutic Agent Toxicity Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific

Interventions

gene expression analysisGENETIC

polymorphism analysisGENETIC

management of therapy complicationsPROCEDURE

Eligibility

Sex: ALLMax age: 20 Years

Medical Language ↔ Plain English

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

Locations (21)

Our Lady's Hospital for Sick Children Crumlin

Dublin, Ireland

Outcomes

Primary Outcomes

CYP3A5 genotype

Renal function and nephrotoxicity

Relationship between CYP3A5 genotype and ifosfamide nephrotoxicity

Secondary Outcomes

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

Data from ClinicalTrials.gov

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