metastatic castration-resistant prostate cancer
Conditions
Interventions
During the prescreening in all patients, 2 x 10 mL blood will be drawn for
enumeration and isolation of CTCs.
All patients with *3 CTCs with AR-V7 expression will be asked to sign consent
for the
end of infusion, 2
and 6 hours after end of the first cabazitaxel infusion) will be drawn for
pharmacokinetic studies, in order to explore a cabazitaxel exposure effect
relation.
Androgen receptor splice variants
Cabazitaxel
Circulating tumor cells
Metastatic castration-resistant prostate cancer
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features. - Continued androgen deprivation therapy either by LHRH agonists/antagonists or orchiectomy. - Serum testosterone
Exclusion criteria
Exclusion criteria: * Geographical, psychological or other non-medical conditions interfering with follow-up * Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus or active systemic or local bacterial, viral, fungal - or yeast infection) * Symptomatic CNS metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent. * Chemotherapy or immunotherapy (other than LHRH analogues) within the last 4 weeks before study inclusion. * Prior treatment with cabazitaxel * Successive treatment with both abiraterone and enzalutamide in the post-docetaxel setting * Radiotherapy to 40% or more of the bone marrow * Known hypersensitivity to corticosteroids * History of severe hypersensitivity reaction (*grade 3) to docetaxel * History of severe hypersensitivity reaction (*grade 3) to polysorbate 80 containing drugs * Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments) (see Appendix C of protocol) * Concomitant vaccination with yellow fever vaccine * Abnormal liver functions consisting of any of the following (within 21 days before treatment group allocation): * Total bilirubin > 1.5 x ULN (except for patients with documented Gilbert's disease) * If total bilirubin > 1 x ULN or AST > 1.5 x ULN inclusion is permitted but cabazitaxel dose should be reduced 20mg/m2 * Abnormal hematological blood counts consisting of any of the following (within 21 days before treatment group allocation): * Absolute neutrophil count
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is PSA response, defined as a *50% PSA decline from baseline during therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints include CTC response, progression-free survival and overall survival to cabazitaxel in AR-V7 positive patients, as well as toxicity and cumulative administered dose of cabazitaxel in second and third-line therapy. Furthermore, we want to explore the relationship between systemic cabazitaxel exposure and response. | — |
Countries
The Netherlands
Outcome results
None listed