Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Dr Gareth Veal


Contact details

Northern Institute of Cancer Research
Paul O'Gorman Building
Framlington Place
Newcastle Upon Tyne
United Kingdom

Additional identifiers

EudraCT number

2008-003606-33 number


Protocol/serial number


Study information

Scientific title

Pilot study to investigate the feasibility of 13-cis-retinoic acid pharmacokinetic monitoring in high-risk neuroblastoma patients


PK 2008 03

Study hypothesis

This study is designed to implement pharmacokinetically guided 13-cis-retinoic acid (Roaccutane) dose adjustment in high-risk neuroblastoma patients. Pharmacokinetic sampling will be carried out on course 1 of treatment and patients who exhibit low drug plasma levels (less than 2 µM), in conjunction with minimal toxicity, will receive an increased dose of 13-cis-retinoic acid on course 2 of treatment. Additional pharmacokinetic sampling will be carried out to monitor plasma concentrations following administration of this increased dose of 13-cis-retinoic acid, again in conjunction with toxicity monitoring. Individualised dosing in patients will then be maintained in order to prevent potentially sub-therapeutic plasma concentrations of 13-cis-retinoic acid being experienced over the remainder of the 13-cis-retinoic acid treatment period. The aim of the study is to achieve consistent plasma concentrations of 13-cis-retinoic acid in high-risk neuroblastoma patients over the 6 month period of treatment.

Ethics approval

Trent Research Ethics Committee approved on the 15/01/2009 (ref: 08/H0405/55)

Study design

Multicentre non-randomised interventional treatment trial

Primary study design


Secondary study design

Non randomised controlled trial

Trial setting

GP practices

Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Topic: National Cancer Research Network; Subtopic: Paediatric Oncology; Disease: Miscellaneous


13-cis-retinoic acid (Isotretinoin) is administered orally to all patients at a dose of 160 mg/m2/day (or 5.33 mg/kg/day for children under 12 kg). A course of treatment lasts for 14 days and patients receive a total of 6 courses, with a 14 day period between each course. Patients who experience peak plasma concentrations of Isotretinoin below 2 µM receive a 25% dose increase on the next course of treatment; patients who experience peak plasma concentrations of Isotretinoin below 1 µM receive a 50% dose increase on the next course of treatment. These dose adjustments are only carried out in patients experiencing minimal or no toxicity.

Depending on the results obtained from course 1, an additional 10 and a further 5 blood samples may be taken on course 2 and 3 respectively. Therefore, a maximum of 20 blood samples may be collected from patients over three courses of treatment.

Blood samples:
Five blood samples will be collected from patients at specific time points over a period of 6 hours following the first dose of 13-cis-retinoic acid administeration on day 14 of course 1 of treatment. In addition, a single blood sample will be taken prior to treatment with 13-cis-retinoic acid for genetic analysis.

Follow up length: 36 months
Study entry: registration only

Intervention type



Not Applicable

Drug names

13-cis-retinoic acid (Roaccutane)

Primary outcome measures

To examine the feasibility of implementing dose individualisation with 13-cis-retinoic acid (Roaccutane) monitoring in patients undergoing treatment. All outcome measures will be measured upon completion of the study.

Secondary outcome measures

1. To ensure that patients are not exposed to potentially sub-optimal plasma concentrations of 13-cis-retinoic acid during long-term treatment
2. To minimize the large inter-patient variation in plasma concentrations of 13-cis-retinoic observed following standard treatment with 13-cis-retinoic acid
3. To obtain preliminary data to investigate the potential impact of 13-cis-retinoic therapeutic monitoring on efficacy and toxicity

All outcome measures will be measured upon completion of the study.

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Age less than 18 years at time of registration, either sex
2. Diagnosis of high-risk neuroblastoma
3. Receiving 13-cis-retinoic acid (Roaccutane) as part of 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
7. A negative pregnancy test for women of childbearing potential, and sexually active patients and partners agreeing to undertake adequate contraceptive measures

Participant type


Age group




Target number of participants

Planned sample size: 75; UK sample size: 75

Participant exclusion criteria

Failure to comply with any of the inclusion criteria

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Northern Institute of Cancer Research
Newcastle Upon Tyne
United Kingdom

Sponsor information


Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)

Sponsor details

Royal Victoria Infirmary
Newcastle upon Tyne
United Kingdom

Sponsor type




Funder type


Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)


Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit


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