Cancer.
Conditions
Interventions
In this open-label crossover pharmacokinetic study, we will compare the plasma pharmacokinetics of irinotecan and its metabolites in patients treated with courses of irinotecan with and without concom
Sponsors
Erasmus MC - Afdeling Interne Oncologie
Eligibility
Inclusion criteria
Inclusion criteria: 1. Histological or cytological confirmed diagnosis of any form of (irresectable and/or metastatic) cancer, which is thought to be sensitive to irinotecan-treatment; 2. Age >= 18 years; 3. WHO performance status 1.5 x 109/L (ANC between 1.5 and 2.0, must be approved by the study coordinators), platelets > 100 x 1012/L); 5. Adequate renal and hepatic functions (serum creatinin < 1.25xULN, bilirubin < 1.25xULN; ALAT and ASAT < 2.5xULN, in case of liver metastasis < 5xULN; alkaline phosphatase < 5xULN; gamma-GT < 5xULN; 6. Written informed consent; 7. Complete initial work-up within two weeks prior to chemotherapy.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating patients; patients with reproductive potential must use a reliable method of contraception (excluding oral contraceptives), if required; 2. Serious illness or medical unstable condition requiring treatment, symptomatic CNS-metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent; 3. Time between last antitumor treatment and first day of irinotecan therapy less than 4 weeks, provided that the patient has recovered from relevant toxic effects; 4. Radiotherapy within the last 4 weeks before the first course, if more than 20% of the bone marrow area is involved; 5. Major surgery within 4 weeks before the first course (to be evaluated by an MD); 6. Unresolved bowel obstruction or chronic colic disease; 7. Unwillingness to abstain from grapefruit(juice), star fruit (carambola), (herbal) dietary supplements, herbal tea, herbals and over-the-counter medication (except for paracetamol and ibuprofen) during the study period (starting two weeks before the first midazolam hydroxylation test); 8. Unwillingness to change medication, or no adequate alternatives available, in case of (chronic) use of CYP3A and/or P-glycoprotein inhibiting or inducing medication, dietary supplements, or other influencing compounds during the study period (starting two weeks before the first midazolam hydroxylation test); 9. Unwillingness to change medication in case of use of midazolam, temazepam and/or diazepam during the study period (starting two weeks before the first midazolam hydroxylation test); 10. Use of omeprazole or any other proton pump inhibitor during the study period (starting two weeks before the first midazolam hydroxylation test).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma pharmacokinetics (PK) of irinotecan and its metabolites. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Side effects, especially neutropenia and late-onset diarrhea; 2. Hepatic CYP3A activity, as determined by the intravenous midazolam hydroxylation test. | — |
Contacts
Public ContactJ.M. Bol, van der
Daniel den Hoed Oncologisch Centrum, Afdeling Interne Oncologie, kamer AS-24. Groene Hilledijk 301
Outcome results
None listed