In this study we therefore investigate the influence of prednisone on docetaxel exposure in metastatic prostate cancer patients.
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the influence of prednisone use on docetaxel pharmacokinetics
compared to docetaxel alone in patients with metastatic castration-resistant
prostate cancer (mCRPC) and metastatic hormone-sensitive prostate cancer
(mHSPC).
Secondary outcome
* To evaluate the incidence and severity of side-effects of treatment with
docetaxel in absence and presence of prednisone.
* Other pharmacokinetic outcomes (i.e. clearance, maximum concentration (Cmax))
Background summary
Co-administration of prednisone with docetaxel is the standard first-line
chemotherapy regimen in men with metastatic castration-resistant prostate
cancer (mCRPC). The use of prednisone as component in the regimen, though, has
remained controversial. A recent report has shown that patients treated with
docetaxel + prednisone experienced less febrile neutropenia compared to
patients treated with only docetaxel.This observation lends further evidence
that a drug-drug interaction between docetaxel and prednisone may alter the
pharmacokinetics (PK) of docetaxel. Docetaxel is mainly metabolized in the
liver by the cytochrome P450, (CYP) 3A4 and 3A5 subfamilies of iso-enzymes, and
prednisone may impact the activity of this metabolic conversion since it*s
known to be a CYP3A4 inducer. Taken together, the possible drug interaction
between taxanes and prednisone may be explained by increased taxane clearance
induced by prednisone, resulting in lower concentrations of circulating drug,
which might ultimately impact drug efficacy and side-effects.
Study objective
In this study we therefore investigate the influence of prednisone on
docetaxel exposure in metastatic prostate cancer patients.
Study design
Patients will be randomized in arm A: to receive 3 cycles of docetaxel plus
prednisone followed by 3 cycles of docetaxel alone or Arm B: 3 cycles of
docetaxel alone followed by 3 cycles of docetaxel plus prednisone. Using this
design, each patient serves as his own control. Pharmacokinetic (PK) blood
samples from docetaxel cycles (75 mg/m2, IV) without prednisone are compared
with PK from the docetaxel cycles with concomitant prednisone (10 mg daily,
PO).
Intervention
none
Study burden and risks
Patients will be exposed to docetaxel chemotherapy + prednisone, which is the
standard therapy in mCRPC and is currently introduced for hormone-sensitive
prostate cancer. Every patient will receive three cycles of docetaxel without
prednisone as well. It is hypothesized that more side-effects of neutropenia
will occur when docetaxel is given without prednisone, with a higher
pharmacokinetic exposure of the cytostatic compound.
The burden for patients participating in this study is a 24-hour hospital
admission during two cycles and additional blood samples for PK analyses during
their admission (12x4mL blood withdrawals during each hospitalizations, so 96mL
in total for the entire study).
Groene Hilledijk 301
Rotterdam 3075EA
NL
Groene Hilledijk 301
Rotterdam 3075EA
NL
Listed location countries
Age
Inclusion criteria
1. Histologicallly or cytologically confirmed adenocarcinoma of the prostate without neuro-endocrine differentitation or small cell features.;2. Continued androgen deprivation therapy either by gonadotropin releasing hormone (GnRH) analogues or orchiedectomy;3. Age *18 years;4. Metastatic disease progression;5. ECOG performance status 0-1;6. Written informed consent according to ICH-GCP
Exclusion criteria
1. Impossibility or unwillingness to take oral drugs;2. Serious concurrent illness or medical unstable condition requiring treatment;3. Symptomatic CNS metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent;4. Known hypersensitivity to studiemedication;5. Use of medication or dietary supplements known to induce CYP3A;6. Any active systemic or local bacterial, viral, fungal - or yeast infection.;7. Abnormal renal function defined as (within 21 days before randomization);8. Abnormal liver functions consisting of any of the following (within 21 days before randomization):;9. Abnormal hematological blood counts consisting of any of the following (within 21 days before randomization):;10. Geographical, psychological or other non-medical conditions interfering with follow-up
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2016-001269-10-NL |
| CCMO | NL58003.078.16 |