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

ConCab compares the standard treatment of cabazitaxel 25 mg/m2 every three weeks with an experimental scheduling of 10 mg/m2 for 5 consecutive weeks of a 6 week cycle. In both study arms the planned cumulative dose of cabazitaxel at week 18 is 150 mg/m2. Our study aims to evaluate differences in the total received dose in relation to the planned dose as a measure of which of the 2 treatment schedules is superior.

Inclusion criteria

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• 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.