metastatic castration-resistant prostate cancer
Conditions
Interventions
In all patients, 2 x 10 mL blood will be drawn for enumeration and isolation of
CTCs at baseline.
If physician's choice is cabazitaxel, cabazitaxel will be administrated
intravenously at a dose of
end of infusion, 2 and 6 hours
after end of infusion) will be drawn for a pharmacokinetic side-study, to
explore a cabazitaxel exposure effect relation.
In patients treated with therapy other than
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 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 <50 ng/ml (1.7 nmol/L) within 21 days of treatment arm allocation. - Age *18 years - Disease progression during or after treatment with docetaxel. Disease progression for study entry is defined as one or more of the following criteria: * At least 3 consecutive PSA rises over a reference value, with an interval of * 1 week between each determination. PSA at screening visit should be * 2.0 *g/l. * Bone disease progression defined by the appearance of *2 new lesions on a bone scan (confirmed by a second bone scan 6 weeks later). * Soft tissue disease progression defined by modified RECIST 1.1. - ECOG performance status 0-2 - Written informed consent according to ICH-GCP
Exclusion criteria
Exclusion criteria: - Impossibility or unwillingness to take oral drugs * 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) * 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 < 1.5 x 109/L * Platelets < 100 x 109/L * Hemoglobin < 6.2 mmol/L
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PSA response defined as a reduction of at least 50% from baseline during therapy, confirmed after *4 weeks by an additional PSA evaluation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints include CTC response rate, progression-free survival and overall survival, as well as toxicity and cumulative administered dose of cabazitaxel in second and third-line therapy. Furthermore, we want to explore the AR-V7 mRNA expression as well as mRNA expression of other splice variants in CTCs. We will also explore the relationship between systemic cabazitaxel exposure and response. Lastly, we want to confirm the impact of the AR-V7 status in CTC on outcome to abiraterone or enzalutamide. | — |
Countries
Netherlands
Outcome results
None listed