To investigate the influence of concomitant enzalutamide on the pharmacokinetics of cabazitaxel.
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cabazitaxel pharmacokinetics (AUC)
Secondary outcome
Toxicity
Cabazitaxel pharmacokinetics (the maximum concentration (Cmax), steady-state
volume of distribution (Vss) and half-life (t*)).
Background summary
Cabazitaxel and enzalutamide are currently registered as standard of care
second line treatment for mCRPC. Concomitant administration of both drugs might
lead to an increased anti tumor effect. However, this drug combination has
never been investigated in humans. Therefore, a drug interaction study has to
be performed before the efficacy can be evaluated.
Study objective
To investigate the influence of concomitant enzalutamide on the
pharmacokinetics of cabazitaxel.
Study design
Fourteen evaluable patients will be enrolled in this crossover trial. Patients
ar their own control, as they will receive cabazitaxel monotherapy during the
first cycle and concomitant enzalutamide during the second and third
cabazitaxel cycle. Pharmacokinetics will be measured clinically up to 24 hours
after cabazitaxel administration and on day 7-9 at the outpatient clinic.
Cabazitaxel pharmacokinetics of the first cycle (monotherapy) will be compared
to pharmacokinetics of the second and third cycle (with concomitant
enzalutamide). After the third cabazitaxel cycle enzalutamide will be
discontinued and cabazitaxel administration will continue as per standard of
care.
Intervention
Cabazitaxel 25 mg/m2 three weekly intravenously, conform standard of care
Enzalutamide 160 mg daily from day 7-9 until day 42 van de studie
Study burden and risks
Patients are admitted to the hospital for 24 hours during three consecutive
(three weekly) cabazitaxel cycles. During these hospital admission blood
withdrawals for pharmacokinetic purposes will be performed, which are
accompanied by a neglgible risk of bleeding or infection. Concomitant
administration of enzalutamide and cabazitaxel might lead to extra toxicity.
However, both drugs have a different spectrum of toxicity and therefore it is
not expected toxicity will increase significantly compared to monotherapy. As a
consequence of CYP3A4 induction by enzalutamide concentrations of cabazitaxel
might decrease temporarily.
's Gravendijkwal 230
Rotterdam 3015 CE
NL
's Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
Age * 18 years
Histological or cytological confirmed diagnosis of mCRPC
ECOG Performance Status * 1
Written informed consent according to ICH-GCP prior to screening evaluations
Indication for cabazitaxel treatmentPatients who are, as per local protocol, eligible for treatment with standard of care cabazitaxel. NB: patients are allowed to have had earlier cabazitaxel cycles
Adequate organ function as defined by:
a.Total bilirubin * 1.5 x ULN (except in case of documented Gilbert*s disease)
b.ASAT * 2.5 x ULN (or * 5 x ULN if liver metastases are present)
c.ALAT * 2.5 x ULN (or * 5 x ULN if liver metastases are present)
d.Serum creatinin * 1.5 x ULN
Exclusion criteria
Evidence of central nervous system disease
History of seizure or any condition predisposing to seizure
Use of concomitant medication predisposing to seizure
Use of (over the counter) medication or (herbal) supplements which can interact with either cabazitaxel or enzalutamide, e.g. by induction or inhibition of CYP3A4, CYP2C9 and CYP2C19 (see appendix B and C)
Unable or unwilling to abstain from grapefruit, grapefruit juice, herbal dietary supplements, and herbal tea during the study
Previous use of enzalutamide during the last 6 weeks prior to cabazitaxel treatment
Contraindications for use of enzalutamide
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-005150-19-NL |
| CCMO | NL51749.078.14 |
| OMON | NL-OMON28269 |