Contact information
Type
Scientific
Primary contact
Dr Gareth Veal
ORCID ID
Contact details
Northern Institute of Cancer Research
Paul O'Gorman Building
Framlington Place
Newcastle Upon Tyne
NE2 4HH
United Kingdom
+44 191 208 4332
g.j.veal@newcastle.ac.uk
Additional identifiers
EudraCT number
2008-003606-33
ClinicalTrials.gov number
NCT00939965
Protocol/serial number
7898
Study information
Scientific title
Pilot study to investigate the feasibility of 13-cis-retinoic acid pharmacokinetic monitoring in high-risk neuroblastoma patients
Acronym
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, 15/01/2009, ref: 08/H0405/55
Study design
Multicentre non-randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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 names
13-cis-retinoic acid (Roaccutane)
Primary outcome measure
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
17/07/2009
Overall trial end date
31/03/2015
Reason abandoned (if study stopped)
Eligibility
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
Patient
Age group
Child
Gender
Both
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
17/07/2009
Recruitment end date
31/03/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Northern Institute of Cancer Research
Newcastle Upon Tyne
NE2 4HH
United Kingdom
Sponsor information
Organisation
Newcastle upon Tyne Hospitals NHS Foundation Trust (UK)
Sponsor details
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK)
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
Basic results (scientific)
Publication list