Condition category
Cancer
Date applied
11/06/2009
Date assigned
27/07/2009
Last edited
27/07/2009
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

Prof Jaap Verweij

ORCID ID

Contact details

Groene Hilledijk 301
Rotterdam
3075 EA
Netherlands

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MEC04-290

Study information

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

Acronym

Study hypothesis

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

Erasmus Medical University Centre Ethics Board approved on the 4th August 2005.

Study design

Multicentre randomised controlled parallel phase II study

Primary study design

Interventional

Secondary study design

Non 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

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

Phase

Phase II

Drug names

Irinotecan

Primary outcome measures

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 trial start date

01/09/2005

Overall trial end date

01/09/2007

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40 evaluable patients

Participant 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.

Recruitment start date

01/09/2005

Recruitment end date

01/09/2007

Locations

Countries of recruitment

Netherlands

Trial participating centre

Groene Hilledijk 301
Rotterdam
3075 EA
Netherlands

Sponsor information

Organisation

Erasmus Medical Centre (Netherlands)

Sponsor details

Groene Hilledijk 301
Rotterdam
3075EA
Netherlands

Sponsor type

Hospital/treatment centre

Website

http://www.erasmusmc.nl/

Funders

Funder type

Hospital/treatment centre

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

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

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