13-cis-retinoic acid monitoring study

ISRCTN	ISRCTN37126758
DOI	https://doi.org/10.1186/ISRCTN37126758
ClinicalTrials.gov (NCT)	NCT00939965
Clinical Trials Information System (CTIS)	2008-003606-33
Protocol serial number	7898
Sponsor	Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
Funder	Cancer Research UK (CRUK) (UK)

Submission date: 18/06/2010
Registration date: 18/06/2010
Last edited: 04/04/2022

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-blood-levels-of-the-drug-13cisretinoic-acid-in-children-and-young-people-with-neuroblastoma

Contact information

Dr Gareth Veal
Scientific

Northern Institute of Cancer Research
Paul O'Gorman Building
Framlington Place
Newcastle Upon Tyne
NE2 4HH
United Kingdom

Phone	+44 191 208 4332
Email	g.j.veal@newcastle.ac.uk

Study information

Primary study design	Interventional
Study design	Multicentre non-randomised interventional treatment trial
Secondary study design	Non randomised controlled trial
Study type	Participant information sheet
Scientific title	Pilot study to investigate the feasibility of 13-cis-retinoic acid pharmacokinetic monitoring in high-risk neuroblastoma patients
Study acronym	PK 2008 03
Study objectives	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(s)	Trent Research Ethics Committee, 15/01/2009, ref: 08/H0405/55
Health condition(s) or problem(s) studied	Topic: National Cancer Research Network; Subtopic: Paediatric Oncology; Disease: Miscellaneous
Intervention	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	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	13-cis-retinoic acid (Roaccutane)
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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.
Completion date	31/03/2015

Eligibility

Participant type(s)	Patient
Age group	Child
Upper age limit	18 Years
Sex	All
Target sample size at registration	75
Total final enrolment	103
Key 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
Key exclusion criteria	Failure to comply with any of the inclusion criteria
Date of first enrolment	17/07/2009
Date of final enrolment	31/03/2015

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Northern Institute of Cancer Research

Newcastle Upon Tyne
NE2 4HH
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	15/01/2013	22/01/2019	Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			04/04/2022	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

04/04/2022: Plain English results and total final enrolment added.
22/01/2019: Publication reference added
18/11/2016: No publications found in PubMed, verifying study status with principal investigator.