Clinical Trial Results:
Pilot study to investigate the feasibility of 13-cis-Retinoic acid pharmacokinetic monitoring in high-risk neuroblastoma
Summary
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EudraCT number |
2008-003606-33 |
Trial protocol |
GB |
Global end of trial date |
19 May 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Mar 2019
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First version publication date |
29 Mar 2019
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Other versions |
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Summary report(s) |
Adaptive dosing approaches to the individualization of 13-cis-retinoic acid (isotretinoin) treatment for children with high-risk neuroblastoma |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PK 2008 03
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Additional study identifiers
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ISRCTN number |
ISRCTN37126758 | ||
US NCT number |
NCT00939965 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Newcastle Upon Tyne Hospitals NHS Foundation Trust
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Sponsor organisation address |
Level 1, Regent Point, Regent Farm Road, Newcastle upon Tyne, United Kingdom, NE3 3HD
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Public contact |
Prof. Gareth J Veal, Northern Institute for Cancer Research, Newcastle University,
Newcastle upon Tyne, NE2 4HH, 44 01912084332, g.j.veal@newcastle.ac.uk
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Scientific contact |
Prof. Gareth J Veal, Northern Institute for Cancer Research, Newcastle University,
Newcastle upon Tyne, NE2 4HH, 44 01912084332, g.j.veal@newcastle.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Dec 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
19 May 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The study is designed as a pilot study to:
•Investigate the feasibility of implementing 13-cis-Retinoic acid dose modification following course 1 of treatment, based on targeted 13-cis-Retinoic acid plasma concentrations and observed toxicity.
• Minimize the large inter-patient variation in plasma concentrations of 13-cis-Retinoic acid observed following standard treatment for high-risk neuroblastoma. This will ensure that patients are not exposed to potentially sub-optimal plasma concentrations of 13-cis-RA during long-term treatment, particularly for those children who are not able to swallow 13-cis-RA capsules.
• Obtain preliminary data investigating the potential impact of 13-cis-RA therapeutic monitoring on clinical response and toxicity in children with high-risk neuroblastoma
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Protection of trial subjects |
Patients receiving the IMP were doing so as part of their standard clinical treatment. Blood volumes for samples taken as part of this trial were kept to a minimum and were taken from the patients central line to minimise pain and distress. Where possible PK samples were taken at the same time as clinical samples to keep discard volumes to a minimum. Participants received age specific participant information sheets so they understood what taking part in the trial involved.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Jul 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 75
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Worldwide total number of subjects |
75
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EEA total number of subjects |
75
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
9
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Children (2-11 years) |
65
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
1
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment period 17/07/2009 to 05/03/2012 UK wide (NHS Sites only). | ||||||
Pre-assignment
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Screening details |
Patients screened by their treating clinician/research nurses as they reach their 13-cis-retinoic acid treatment period (standard care) against the inclusion criteria stated in the protocol. Patients only excluded during screening if they fail to meet the study inclusion criteria. | ||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
Arms
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Arm title
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Overall trial | ||||||
Arm description |
Overall trial | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Roaccutane
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Investigational medicinal product code |
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Other name |
13-cis-retinoic acid, Isotretinoin
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Maximum dose 240mg/m2/day.
Start dose 160mg/m2/day given over 2 divided doses for 14 days followed by 14 days drug free (1 cycle), typically 6 cycles of treatment.
Dose adjustments were carried out on cycle 2 with dose increases of 25% and 50% in patients with peak plasma concentrations of <2.0µM and <1.0µM respectively.
Children less than 12kg received a reduced starting dose of 5.33mg/kg/day.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Overall trial |
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End point title |
Quantification of Roaccutane plasma levels [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Drug levels measured on multiple courses of treatment for each patient until target level reached
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: End point was determined by a defined cut off point which patients fell either above or below. No statistical analysis directly related to the primary endpoint required. |
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Notes [2] - Values obtained for all patients |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Per patient - from start of recruitment to 1 month after final cycle of treatment for which PK monitoring is carried out.
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Adverse event reporting additional description |
Only adverse events directly related to PK sampling were collected for this trial.
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
NCI CTC | ||
Dictionary version |
4
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Frequency threshold for reporting non-serious adverse events: 5% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There were no reported non serious adverse events recorded. Only adverse events related to PK sampling from the central line are required to be reported. All other AE's are reported via the main clinical trial the patient is being treated on. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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19 Oct 2009 |
Change of sponsor from University Hospitals of Leicester NHS Trust to Newcastle upon Tyne Hospitals NHS Foundation Trust. Change in study sponsor accompanied by change in study management to the Northern Institute for Cancer Research, Newcastle University from the CCLG Data Centre in Leicester. Protocol changes relate to change of sponsor and study management only (New protocol version 2.0). |
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29 Jun 2010 |
Change of Principal Investigator at Birmingham Children's Hospital. No changes to protocol. |
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26 Jul 2010 |
Change of Principal Investigator at Nottingham University Hospitals. No changes to protocol. |
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15 Aug 2011 |
Addition of a new site, the Royal Hospital for Sick Children, Edinburgh and new Principal Investigator. No changes to protocol. |
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15 Mar 2012 |
Change of Principal Investigator at Southampton University Hospital NHS Foundation Trust. No changes to protocol. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/23087409 |