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

A Randomized, Open Label, Multicenter, Phase II Trial Comparing The Conventional 3 Weekly Schedule Of Cabazitaxel With A Weekly Regimen In Patients With Metastatic Castration Resistant Prostate Cancer

Cabazitaxel has shown significant efficacy as second line chemotherapy after Docetaxel in men with metastatic castration resistant prostate cancer. This was demonstrated in the Tropic Study where Cabazitaxel showed survival superiority compared to mitoxantrone. Almost one in 4 patients treated with Cabazitaxel in this study required dose reductions or dose delays or stopped treatment due to toxicity. ConCab examines another scheduling for cabazitaxel to see if we can improve tolerability so that patients will receive a higher percentage of the treatment as planned.

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:¨

• 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.