CYP3A4 phenotype-based dosing of irinotecan

ISRCTN	ISRCTN84131514
DOI	https://doi.org/10.1186/ISRCTN84131514
Secondary identifying numbers	MEC04-290

Submission date: 11/06/2009
Registration date: 27/07/2009
Last edited: 27/07/2009

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Jaap Verweij
Scientific

Groene Hilledijk 301
Rotterdam
3075 EA
Netherlands

Study information

Study design	Multicentre randomised controlled parallel phase II study
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A new dosing strategy to lower inter-patient variability of irinotecan pharmacokinetics in cancer patients: a two-centre randomised controlled parallel phase II study
Study objectives	The use of an irinotecan dosing strategy based on a formula derived from the midazolam clearance test, gamma-glutamyl transpeptidase (gamma-GT) and height, should lower inter-patient variability in first course pharmacokinetics in cancer patients, compared to a classic dose-strategy based on body-surface area (BSA).
Ethics approval(s)	Erasmus Medical University Centre Ethics Board approved on the 4th August 2005.
Health condition(s) or problem(s) studied	Cancer
Intervention	1. Single midazolam clearance test (MCT), involving midazolam infusion and pharmacokinetic measurements 2. Regular laboratory testing prior to irinotecan infusion, and weekly outpatients controls 3. Irinotecan infusion (90 minutes intravenously [iv] every three weeks [q3w]) and irinotecan pharmacokinetic measurements during the first course (3 weeks) For the irinotecan infusion, patients were divided into two groups: Group A: patients received a dose of irinotecan based on the new formula Group B: patients received a dose based on classic body surface area (BSA) -based dosing The course of chemotherapy was given in 90 minutes, once every three weeks. During those 3 weeks extra blood samples for pharmacokinetic analyses were taken and toxicity measures (i.e. neutropenia) were scored. After that one course, there was no follow-up.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Irinotecan
Primary outcome measure	Pharmacokinetics (AUC/clearance) of midazolam, irinotecan and metabolite SN-38, determined by LC-MS-MS and calculated using WinNonlin, measured during the infusion period and for the next 3 weeks
Secondary outcome measures	Toxicity assessment (i.e. leukopenia, neutropenia, neutropenic fever, diarrhoea), measured during the infusion period and for the next 3 weeks
Overall study start date	01/09/2005
Completion date	01/09/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	40 evaluable patients
Key inclusion criteria	1. Histological or cytological confirmed diagnosis of any form of cancer, which is thought to be sensitive to irinotecan-treatment 2. Aged 18 years or older, either sex 3. World Health Organization (WHO) performance status 0 or 1 4. Adequate haematological functions, as determined 2 weeks before inclusion and within 2 days before start of irinotecan infusion (neutrophil count greater than 2.0 x 10^9/l, platelets greater than 100 x 10^9/L) 5. Adequate renal and hepatic functions, as determined 2 weeks before inclusion and within 2 days before start of irinotecan infusion (bilirubin less than 1.25 x upper limit of normal [ULN]; serum glutamic oxaloacetic transaminase [SGOT]/serum glutamic pyruvate transaminase [SGPT] less than 2.5 x ULN, in case of liver metastasis less than 5 x ULN; serum creatinine less than 1.25 x ULN; alkaline phosphatase [AP] less than 5 x ULN; gammaGT less than 200 U/l) 6. Written informed consent 7. Complete workup within 2 weeks prior to chemotherapy
Key exclusion criteria	1. Pregnant or lactating patients 2. Other serious illness or medical unstable conditions requiring treatment 3. Symptomatic central nervous system (CNS) metastases 4. History of psychiatric disorder 5. Time between last anti-tumour chemotherapy treatment and first day of irinotecan therapy less than 4 weeks 6. Radiotherapy within 4 weeks before chemotherapy, unless less than 20% of bone marrow area is involved 7. (Recent) radiotherapy at abdomen 8. Major surgery within 4 weeks before study entry 9. Unresolved bowel obstruction or chronic colic disease 10. Use of, and unwillingness to abstain from grapefruit (juice), herbal supplements/tea/over the counter medicines during the study period (starting 3 weeks before the first course). (Chronic) use of CYP3A and Pgp inhibiting/inducing medication, dietary supplements, or other inhibiting compounds.
Date of first enrolment	01/09/2005
Date of final enrolment	01/09/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

Groene Hilledijk 301

Rotterdam
3075 EA
Netherlands

Sponsor information

Erasmus Medical Centre (Netherlands)
Hospital/treatment centre

Groene Hilledijk 301
Rotterdam
3075EA
Netherlands

Website	http://www.erasmusmc.nl/
"ROR"	https://ror.org/018906e22

Funders

Funder type

Hospital/treatment centre

Pfizer Inc. (Netherlands) - provided medication; no financial support

No information available

Erasmus Medical Centre (Netherlands) - Daniel den Hoed Kliniek covered costs for pharmacokinetic measurements

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan