Cabazitaxel in mCRPC Patients With AR-V7 Positive CTCs

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 before treatment group 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:

    * PSA progression defined by at least 2 consecutive PSA rises over a reference value, with an interval of ≥ 1 week between each determination. PSA at screening visit should be ≥ 2.0 μg/l.
    * Bone disease progression defined by the appearance of new lesions on a bone scan, confirmed on a second bone scan ≥ 6 weeks later.
    * Soft tissue disease progression defined by modified RECIST criteria 1.1 (baseline LN size must be ≥ 2.0 cm to be considered target or evaluable lesion) (15)
  * ECOG performance status 0-2 (appendix A)
  * Written informed consent according to ICH-GCP before study treatment and any study specific procedures

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