To determine the exposure and clearance of intravenous docetaxel in patients with castration-resistant prostate cancer and non-castration-resistant prostate cancer. All samples will be measured with a validated LC-MS/MS method
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To compare the clinical pharmacokinetics, specifically exposure and total
plasma clearance, of docetaxel between castration-resistant prostate cancer
patients and non-castration-resistant prostate cancer patients.
Secondary outcome
• To measure plasma concentrations of docetaxel metabolites M1, M2, M3 and M4
• To determine metabolite pharmacokinetics
• To determine androgen levels in the predose sample and to explore the
correlation between androgen levels and docetaxel pharmacokinetics
• To determine α1-acid glycoprotein levels and the free fraction of docetaxel
at timepoints t=1h and t=48h and to explore the correlation between these
levels and docetaxel pharmacokinetics
• To establish the effect of functional genetic polymorphisms on the
pharmacokinetics of docetaxel (21)
• To compare the pharmacokinetics of docetaxel in patients with prostate cancer
(both castration-resistant and non-castration-resistant) with literature
docetaxel pharmacokinetics in patients with a different solid tumor type
Background summary
The pharmacokinetics of docetaxel are characterized by substantial
interindividual variability. Altered docetaxel pharmacokinetics are reported in
patients with castration-resistant prostate cancer and non-castration-resistant
prostate cancer, with a 2-fold higher clearance and 2-fold lower area under the
curve (AUC) in castration-resistant patients. Presumably, long-term castrate
levels of testosterone or the castration-resistant phase of disease cause an
increased elimination of docetaxel. The mechanism behind this remains to be
elucidated. However, several explanations for increased clearance are given in
literature, such as CYP3A4-induction, P-glycoprotein (P-gp, ABCB1) induction,
rOat2 induction and 1α-acid glycoprotein induction.
Study objective
To determine the exposure and clearance of intravenous docetaxel in patients
with castration-resistant prostate cancer and non-castration-resistant prostate
cancer. All samples will be measured with a validated LC-MS/MS method
Study design
After obtaining informed consent, blood will be drawn for pharmacokinetic
analysis after routine administration of docetaxel
Intervention
not applicable
Study burden and risks
Patients participating will be hospitalized for 1 day. Blood sampling for
pharmacokinetic research is done at 8 time points. As docetaxel is standard of
care treatment for this patient population, no additional risk is expected to
be associated with study participation.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
1. Histological or cytological metastatic prostate cancer with an indication for systemic treatment with intravenous docetaxel at the discretion of the physician
Planned to receive first time docetaxel for prostate cancer.
• Group 1: Metastatic castration-resistant prostate cancer with progressive disease defined as biochemical and/or radiological progression according to the Prostate Cancer Working group 3 recommendations. (4) These patients have progressive disease despite long term treatment with hormonal therapy, so they have longterm castrate levels of testosterone. Docetaxel is started after progression on hormonal therapy.
• Group 2: Non-castration-resistant metastatic prostate cancer with an indication for first line docetaxel according to standard clinical care. These patients have metastatic disease at diagnosis and they receive their first systemic treatment as a combined treatment with hormonal therapy and docetaxel. The hormonal therapy is started between 12 and 4 weeks prior to the start of docetaxel. Therefore these patients have castrate levels of testosterone at the start of docetaxel.
2. Considered fit for docetaxel treatment as assessed by the treating physician.
3. Castrate levels of testosterone, defined as <= 50 ng/dL (or <= 0.50 ng/mL or 1.73 nmol/L)
4. Age >= 18 years.
5. Able and willing to give written informed consent.
6. Able and willing to undergo blood sampling for PK and pharmacogenetics analysis.
7. Able and willing to comply with study restrictions and to remain at the study center for the required duration.
8. Adequate organ system function.
Exclusion criteria
not applicable
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL63555.031.17 |