Pharmacokinetic variation and toxicity in Ewing's sarcoma

Not Applicable

Completed

• Conditions: Ewing's sarcoma; Cancer

• Registration Number: ISRCTN52616678
• Lead Sponsor: The Newcastle Upon Tyne Hospitals NHS Foundation Trust (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-02-25
• Study Completion: 2023-11-20
• Last Update Posted: 20 November 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 139

Inclusion Criteria

1. Age 0 - 24 years
2. Diagnosis of histologically confirmed Ewing sarcoma
3. Receiving VIDE or VDC/IE as part of standard clinical treatment
4. Single or double lumen central venous catheter in place
5. Written informed consent
6. Protocol approval by national and local ethics committee, regulatory authority and Trust R&D Departments

Exclusion Criteria

1. Receiving nonstandard dose chemotherapy.
2. Glomerular filtration rate <60 ml/min/1.73m2.

Study & Design

• Study Type: Observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. To establish pharmacokinetic profiles for vincristine, ifosfamide, doxorubicin, etoposide and cyclophosphamide in adolescent Ewing's sarcoma patients and to compare profiles between children, adolescents and adults. Pharmacokinetic measurements will be performed on one course of treatment using established methods for the measurement of vincristine, ifosfamide, doxorubicin, etoposide and cyclophosphamide by liquid chromatography/mass spectrometry (LC/MS).<br> 2. To validate in young people a panel of blood-borne biomarkers which have been shown to be predictive of bone marrow and mucosal toxicity in adults. Blood samples for biomarker analysis will be taken on cycles 1, 2 and the last cycle of induction chemotherapy. M30 and M65 ELISA assays will be performed as biomarkers for mucosal toxicity. The FLT 3 ligand assay will be performed as a biomarker for bone marrow toxicity.<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. To examine polymorphisms associated with drug metabolism and identify loci associated with the major acute and late toxicities associated with VIDE or VDC/IE chemotherapy.<br> 2. To investigate potential relationships between pharmacokinetics, biomarkers of toxicity and pharmacogenetics in Ewing's sarcoma patients.<br><br> A single blood sample for pharmacogenetic analysis taken prior to the first course of VIDE or VDC/IE treatment, will be used to investigate whether genetic variation in the expression of key enzymes could underlie individual differences in drug metabolism and exposure.<br>