Condition category
Cancer
Date applied
14/12/2008
Date assigned
06/10/2009
Last edited
30/08/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Kimmo Murto

ORCID ID

Contact details

Children's Hospital of Eastern Ontario
401 Smyth Road
Ottawa
K1H8L1
Canada
+1 613 737 2431
Kmurto@cheo.on.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

18/08SE

Study information

Scientific title

The impact of genotype on plasma and cerebral spinal fluid pharmacokinetics of celecoxib in children: a randomised controlled single-centre trial

Acronym

Study hypothesis

1. The cerebral spinal fluid (CSF) concentration of celecoxib 3 hours post oral suspension ingestion is lower than plasma levels
2. The CSF peak concentration (Cmax) of celecoxib is delayed compared to plasma Cmax
3. The CSF concentration of celecoxib is directly related to the dose ingested and underlying P450 genotype
4. Blood and CSF celecoxib concentration is directly related to age
5. Oral celecoxib dosage is directly related to quality of life and inversely related to level of discomfort when administered prior to and one dose after a lumbar puncture (LP) +/- bone marrow biopsy (BM)

Ethics approval

Children's Hospital of Eastern Ontario (CHEO) Research Ethics Board (ref: 09/10E). Approval pending as of 31/03/2009.

Study design

Randomised controlled single-centre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Haematological malignancy

Intervention

Cohort receives oral celecoxib 10 mg/kg 3 hours prior to first scheduled LP (LP 1) and then 5 mg/kg 12 hours after first dose and multiple blood samples to create blood PK profile. Randomisation into one of two groups (Group 1: CSF dose timing; Group 2: dose variation) prior to undergoing the remaining scheduled LPs (LPs 2-5).

Group 1: Oral celecoxib 10 mg/kg either 60, 120, 300 or 900 mins prior to remaining 4 LPs followed by 5 mg/kg post first dose to create CSF PK profile.

Group 2: Either oral celecoxib 6 mg/kg or 14 mg/kg on 2 occasions each 3 hours before LP and then 12 hours later to create truncated CSF and blood PK profiles at higher and lower doses.

Intervention type

Drug

Phase

Phase IV

Drug names

Celecoxib

Primary outcome measures

1. All patients and CSF dose timing cohort (Group 1: Oral celecoxib 10 mg/kg pharmacokinetic profile)
1.1. Mean total and unbound plasma concentration ug/L at approximately the following time intervals (mins): 30, 60, 90, 120, 180, 300, 900
1.2. Mean CSF concentration ug/L at approximately the following time intervals (mins): 60, 120, 180, 300, 900
1.3. Ratio CSF/unbound plasma concentration at approximately the following time intervals (mins): 60, 120, 180, 300, 900
1.4. This information will be used to determine plasma and CSF mean +/- SD values for maximum concentration (Cmax [ug/L]); area under concentration curve from time 0 to infinity; apparent oral volume of distribution (Vd/F [L/kg]); apparent oral clearance (CL/F [L·h-1·kg-1] and terminal elimination half-life (t1/2 [h]). A median value will be determined for time to maximum concentration (tmax[h]).

2. Dose escalation cohort (Group 2: Oral celecoxib 6 mg/kg and 14 mg/kg pharmacokinetic profile)
2.1. Mean total and unbound plasma concentration ug/L at approximately the following time intervals (mins): 60, 180, 300
2.2. Mean CSF concentration ug/L at approximately 180 min
2.3. Ratio CSF/unbound plasma concentration at approximately 180 min
2.4. This information in conjunction with the pharmacokinetic profile established in the dose timing cohort (10 mg/kg) will be used to predict plasma and CSF values for tmax, Cmax, AUC, Vd/F, CL/F and t1/2 for 6 and 14 mg/kg oral doses respectively.

Secondary outcome measures

1. Polymorphisms of genotypes CYP2C9 and CYP3A4 liver enzymes and correlations to drug levels
2. Pediatric Quality of life Inventory (PedsQL) version 4.0 scores before and 7 days after LP
2.1. Parent report for children aged 2-7, 8-12 and 13-18
2.2. Child report ages 8-12 and 13-18
3. PedsQL Cancer module version 3.0 scores before and 7 days after LP
3.1. Parent report for children aged 2-7, 8-12 and 13-18
3.2. Child report ages 8-12 and 13-18
4. PedsQL Multidimension Fatigue Scale version 1.0 scores before and 7 days after LP
4.1. Parent report for children aged 2-7, 8-12 and 13-18
4.2. Child report ages 8-12 and 13-18
5. PedsQL Pediatric Pain Questionnaire baseline and daily scores for 7 days after LP
5.1. Parent report for children aged 2-7, 8-12 and 13-18
5.2. Child report ages 5-7, 8-12 and 13-18
6. Demographics including professional identity of the individual performing the LP+/-BM, description of the LP and BM needles used, number of attempts and degree of difficulty
7. Adverse events recorded daily for 7 days after each dose ingested

Overall trial start date

01/04/2009

Overall trial end date

01/10/2011

Reason abandoned

Eligibility

Participant inclusion criteria

Both males and females, age 2-18 years with haematological malignancy expected to undergo five lumbar punctures.

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

20

Participant exclusion criteria

1. Serum creatinine >2 X upper normal limit (UNL)
2. Abnormal liver function; namely alanine aminotransferase (ALT) >1.5 X UNL, alkaline phosphatase (ALP) > 5X UNL, total bilirubin >2 X UNL
3. History of peptic ulcer disease
4. Allergy to celecoxib, sulfonamide compounds or non steroidal anti-inflammatory drugs (NSAIDs)
5. Patients receiving CYP2C9 inhibitors fluconazole, amiodarone and oxandrolone
6. Patients receiving CYP2C9 inducers rifampin and phenobarbitol
7. Extremes of body mass index (BMI) (age related below 10th or above 90th percentile)
8. Parents of any participants, irrespective of age, who are unable to read and understand instructions relayed in English or French
9. Participant and/or parents of any participants, irrespective of age, who suffer from dementia, psychosis, significant developmental delay or other impairment that would prohibit the understanding and giving of informed consent or assent or the participation in self-care or toxicity reporting

Recruitment start date

01/04/2009

Recruitment end date

01/10/2011

Locations

Countries of recruitment

Canada

Trial participating centre

Children's Hospital of Eastern Ontario
Ottawa
K1H8L1
Canada

Sponsor information

Organisation

Children's Hospital of Eastern Ontario Research Institute (Canada)

Sponsor details

401 Smyth Road
Rm. 139
Ottawa
Ontario
K1H 8L1
Canada

Sponsor type

Hospital/treatment centre

Website

http://www.cheori.org/

Funders

Funder type

University/education

Funder name

University of Ottawa, Department of Anesthesiology, Chairman's Fund (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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