Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Gareth Veal
ORCID ID
Contact details
Northern Institute for Cancer Research
Paul O'Gorman Building
Newcastle University
Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom
+44 (0)191 208 4332
g.j.veal@ncl.ac.uk
Additional identifiers
EudraCT number
2013-000052-17
ClinicalTrials.gov number
Protocol/serial number
PK 2013 01
Study information
Scientific title
Pilot study to investigate the early prediction of toxicity following induction chemotherapy in Ewings sarcoma by blood-borne biomarkers and correlation with age-dependent pharmacokinetic variation
Acronym
Study hypothesis
The main objective behind this study is to test the hypothesis that the variation seen in the exposure to vincristine, ifosfamide, cyclophosphamide, doxorubicin and etoposide in patients is related to the age of the patient (children, adolescents and adults). This may explain differences in toxicity and/or survival response to these drugs.
Ethics approval
National Research Ethics Service committee North East - Newcastle and North Tyneside 1, 07/10/2013, Ref: 13/NE/0225
Study design
Five year observational pharmacology study
Primary study design
Observational
Secondary study design
Other
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Cancer/Ewing's sarcoma/Paediatrics and young adults
Intervention
The study will involve 120 male and female Ewing's sarcoma patients recruited at 20 clinical cancer centres across the UK. Participation will be over a five-year period.
Blood sampling for pharmacokinetic studies will taken over a maximum period of 24 h or 54 h depending on the treatment arm. Blood sampling for biomarkers will be collected on 4 separate study days. Patients will be followed up clinically for a period of 3 years.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
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).
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.
Secondary outcome measures
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.
2. To investigate potential relationships between pharmacokinetics, biomarkers of toxicity and pharmacogenetics in Ewing's sarcoma patients.
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.
Overall trial start date
01/02/2014
Overall trial end date
31/01/2019
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
120
Participant exclusion criteria
1. Receiving nonstandard dose chemotherapy.
2. Glomerular filtration rate <60 ml/min/1.73m2.
Recruitment start date
01/02/2014
Recruitment end date
31/01/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Northern Institute for Cancer Research
Newcastle upon Tyne
NE2 4HH
United Kingdom
Sponsor information
Organisation
The Newcastle Upon Tyne Hospitals NHS Foundation Trust (UK)
Sponsor details
c/o Andrew Johnston (RM&G Manager)
Joint Research Office
Level 6 Leazes Wing
Royal Victoria Infirmary
Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom
+44 (0)191 282 5969
andrew.johnston@nuth.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (C27826/A15994)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary