Pharmacokinetic variation and toxicity in Ewing's sarcoma

ISRCTN	ISRCTN52616678
DOI	https://doi.org/10.1186/ISRCTN52616678
EudraCT/CTIS number	2013-000052-17
Secondary identifying numbers	PK 2013 01

Submission date: 14/01/2014
Registration date: 25/02/2014
Last edited: 26/06/2025

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-blood-levels-of-chemotherapy-drugs-in-people-with-ewings-sarcoma-pk201301

Contact information

Dr Gareth Veal
Scientific

Northern Institute for Cancer Research
Paul O'Gorman Building
Newcastle University
Medical School
Framlington Place
Newcastle upon Tyne
NE2 4HH
United Kingdom

Phone	+44 (0)191 208 4332
Email	g.j.veal@ncl.ac.uk

Study information

Study design	Five-year observational pharmacology study
Primary study design	Observational
Secondary study design	Other
Study setting(s)	Hospital
Study type	Diagnostic
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Pilot study to investigate the early prediction of toxicity following induction chemotherapy in Ewing's sarcoma by blood-borne biomarkers and correlation with age-dependent pharmacokinetic variation
Study objectives	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(s)	National Research Ethics Service committee North East - Newcastle and North Tyneside 1, 07/10/2013, Ref: 13/NE/0225
Health condition(s) or problem(s) studied	Ewing's sarcoma
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
Primary outcome measure	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 study start date	01/02/2014
Completion date	31/12/2025

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	0 Years
Upper age limit	24 Years
Sex	Both
Target number of participants	120
Total final enrolment	139
Key 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
Key exclusion criteria	1. Receiving nonstandard dose chemotherapy. 2. Glomerular filtration rate <60 ml/min/1.73m2.
Date of first enrolment	01/02/2014
Date of final enrolment	20/11/2020

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Northern Institute for Cancer Research

Newcastle upon Tyne
NE2 4HH
United Kingdom

Sponsor information

The Newcastle Upon Tyne Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

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
England
United Kingdom

Phone	+44 (0)191 282 5969
Email	andrew.johnston@nuth.nhs.uk
"ROR"	https://ror.org/05p40t847

Funders

Funder type

Charity

Cancer Research UK (C27826/A15994)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date	30/06/2026
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	The datasets generated during and/or analysed during the current study will be available upon request from Professor Gareth Veal (g.veal@nhs.net). Participants have not given consent for sharing of data – therefore, only selected anonymised individual participant data that underlie the results reported in the article will be available. The trial protocol will also be available. Data will be available following article publication. Only investigators whose proposed use of the data has been approved by an independent review committee will be granted access to the data via ‘password protected’ documents sent to an individual email account. Proposals shall be directed to Professor Gareth Veal. To gain access requestors will need to sign a data access agreement.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Plain English results			26/06/2025	No	Yes

Editorial Notes

26/06/2025: Cancer Research UK plain English results link added.
09/04/2025: The overall study end date has been changed from 20/04/2025 to 31/12/2025. The intention to publish date was changed from 31/12/2025 to 30/06/2026.
10/01/2025: The overall study end date has been changed from 20/11/2023 to 20/04/2025. The intention to publish date was changed from 01/10/2024 to 31/12/2025.
06/11/2023: The IPD sharing plan has been added.
02/10/2023: The following changes have been made:
1. The recruitment end date has been changed from 01/04/2019 to 20/11/2020.
2. The overall study end date has been changed from 01/10/2023 to 20/11/2023.
3. The final enrolment number has been added.
08/05/2019: The following changes were made to the trial record:
1. The overall end date was changed from 01/04/2022 to 01/10/2023.
2. The intention to publish date was added.
10/06/2018: The overall trial end date has been changed from 31/01/2019 to 01/04/2022
06/08/2018: The recruitment end date was changed from 31/01/2019 to 01/04/2019