prostate cancer and other types of solid tumours
Conditions
Interventions
On day 1, oral midazolam (2 mg) will be administered, followed by PK sampling
until 8 hours postdose
On day 2, intravenous midazolam (1 mg) will be administered, followed by PK
sampling until 8 hour
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male patients receiving anticancer treatment or supportive care within our institute • Group 1: histological or cytological proof of prostate cancer, for which the treatment leads to castrate levels of testosterone, defined as = 18 years. 4. Able and willing to give written informed consent. 5. Able and willing to undergo blood sampling for PK and pharmacogenetic analysis. 6. Able and willing to comply with study restrictions and to remain at the study center for the required duration. 7. Adequate bone marrow, hepatic and renal functions
Exclusion criteria
Exclusion criteria: 1. Concomitant use of medication, herbs or food which could influence the pharmacokinetics of midazolam within 14 days or five half-lives of the drug (whichever is shorter) before start of the study, consisting of (but not limited to) CYP3A4-inhibitors/inducers. In particularly, use of enzalutamide, bicalutamide and dexamethasone is not allowed within 14 days before start of the study. The use of prednisolone is allowed at a maximum daily dose of 10 mg. 2. Current smokers or patients who stopped smoking within 7 days before study allocation 3. Cachexia as evaluated by a modified Glasgow Prognostic Score (mGPS) of 2: albumin = 10 mg/L 4. Patients with a known psychological or physical condition and/or expected poor prognosis, which in the opinion of the investigator, contra-indicates hospitalization and/or participation in the study for the individual patient.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the CYP3A4 activity in prostate cancer patients versus patients with other types of solid tumours, by use of a midazolam phenotyping test | — |
Secondary
| Measure | Time frame |
|---|---|
| - To measure plasma concentrations of midazolam - To determine metabolite pharmacokinetics of midazolam - Since polymorphisms in genes encoding for CYP3A4 can be important determinants in the pharmacokinetics of midazolam, single nucleotide polymorphisms in these genes will be assessed retrospectively - exploratory: to differentiate between hepatic and gastro-intestinal CYP3A4 activity by comparison of oral and intravenous midazolam PK | — |
Countries
Netherlands
Outcome results
None listed