A Study Looking at Novel Scheduling of Cabazitaxel for Patients With Metastatic Prostate Cancer

Inclusion Criteria:¨

* Histological confirmed prostate cancer
* Macroscopic metastatic disease
* Prior treatment with Docetaxel
* Castration resistant disease defined as:Serum testosterone (\< 0.5 ng/ml) and:
* Increase in measurable disease (RECIST 1.1, see appendix 10) or
* For non-measurable disease, the appearance of at least one new lesion on nuclear scintigraphy) or
* A rising PSA from the previous reference value on 2 consecutive occasions at least one week apart
* Written informed consent

Exclusion Criteria:

* Less than 21 days since prior treatment with chemotherapy
* Less than 14 days since radiotherapy or surgery to the start of cabazitaxel - Less than 4 weeks after stopping endocrine therapies including antiandrogen, abiraterone or other new agents.
* Prior isotope therapy or radiotherapy to \> 30% of bone marrow (whole pelvic radiotherapy is not an exclusion criteria)
* Persistent adverse events from previous cancer therapies \> grade 1 (CTCAE - Version 4.0) with the exception of alopecia. (With respect to peripheral neuropathy and nail changes grade 2 is acceptable)
* ECOG performance status \> 1
* Known CNS malignancy
* Within 6 months of randomization:

  * myocardial infarction,
  * unstable angina,
  * angioplasty,
  * bypass surgery,
  * stroke,
  * TIA, or
  * congestive heart failure NYHA class III or IV
* Within 3 months prior to randomization:

  * treatment resistant peptic ulcer disease,
  * infectious or inflammatory bowel disease,
  * pulmonary embolism
  * Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretation of study results
* History of hypersensitivity to docetaxel or polysorbate 80
* Inadequate organ and bone marrow function as evidenced by:

  * Hemoglobin \< 9.0 g/dL
  * Absolute neutrophil count \< 1.5 x 109/L,
  * Platelet count \< 100 x 109/L,
  * AST/SGOT and/or ALT/SGPT \> 1.5 x ULN;
  * Total bilirubin \> 1.0 x ULN,
  * Serum creatinine \> 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance \< 60 mL/min should be excluded (http://mdrd.com/ for on-line calculation)
* Concurrent or planned treatment with potent inhibitors or inducers of cytochrome P450 3A4/5. A one week wash out period is necessary for patients who are already on these treatments.
* Patients with reproductive potential not implementing accepted and effective method of contraception.