Condition category
Cancer
Date applied
14/01/2014
Date assigned
25/02/2014
Last edited
29/04/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 Ewing’s 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)

CRUK

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

Publication citations

Additional files

Editorial Notes