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

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00514345
• Other study ID #: CCLG-PK-2007-02
• Secondary ID: CDR0000560128EU-
• Status: Recruiting
• Phase: N/A
• First received: August 8, 2007
• Last updated: August 9, 2013
• Start date: July 2007

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 20 Years

Eligibility

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

Study Design

N/A

Related Conditions & MeSH terms

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

Intervention

Genetic:
• gene expression analysis

• polymorphism analysis

Procedure:
• management of therapy complications

Locations

Country	Name	City	State
Ireland	Our Lady's Hospital for Sick Children Crumlin	Dublin
United Kingdom	Royal Aberdeen Children's Hospital	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Bristol Royal Hospital for Children	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Childrens Hospital for Wales	Cardiff	Wales
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children	London	England
United Kingdom	University College Hospital	London	England
United Kingdom	Royal Manchester Children's Hospital	Manchester	England
United Kingdom	Sir James Spence Institute of Child Health at Royal Victoria Infirmary	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
Children's Cancer and Leukaemia Group

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CYP3A5 genotype			No
Primary	Renal function and nephrotoxicity			Yes
Primary	Relationship between CYP3A5 genotype and ifosfamide nephrotoxicity			Yes
Secondary	Comparison of measured glomerular filtration rate (GFR) with the Cole model			No