Cabazitaxel and Prednisone in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

PRIMARY OBJECTIVES:

I. To test whether men with a poor initial response to androgen deprivation therapy (ADT)
have a better front line therapeutic response to cabazitaxel as compared to historical
controls of frontline metastatic castrate resistant prostate cancer (CRPC) therapy with
abiraterone or enzalutamide.

SECONDARY OBJECTIVES:

I. To determine the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
response rate, progression free survival (PFS) by Prostate Cancer Clinical Trials Working
Group 2 (PCWG2) criteria, and overall survival (OS).

II. To evaluate safety and toxicity profile of cabazitaxel in patients with CRPC.

TERTIARY OBJECTIVES:

I. To collect serum and tumor tissue samples for molecular markers or signature predictive of
cabazitaxel benefit (to include status of androgen receptor [AR] pathway, androgen
biosynthetic pathway genes, adenosine triphosphate [ATP]-binding cassette sub-family B member
1 [ABCBI], multidrug resistance-associated protein 1 [MRP1], and other mediators of taxane
resistance).

OUTLINE:

Patients receive cabazitaxel intravenously (IV) over 1 hour on day 1 and prednisone orally
(PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 6 courses in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Inclusion Criteria:

- Histologically confirmed prostate adenocarcinoma

- Metastatic disease

- Able and willing to provide informed consent and to comply with the study procedures

- Castration resistant disease defined as evidence of radiological and/or prostate
specific antigen (PSA) progression despite castrate levels of testosterone (serum
testosterone < 50 ng/dL [1.7 nmol/L]); for PSA progression, there must be at least 2
sequential rises at a minimum of 1-week intervals; the first PSA value must be >= 4
(Prostate Cancer Working Group 2 [PCWG2] criteria)

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- At least 21 days have passed since completing radiotherapy (exception for
radiotherapy: at least 7 days since completing a single fraction of =< 800 cGy to a
restricted field or limited-field radiotherapy to non-marrow bearing area such as an
extremity or orbit) at the time of registration

- At least 21 days have passed since receiving any investigational agent at the time of
registration

- At least 21 days have passed since major surgery

- Neuropathy =< grade 1 at the time of registration

- Has recovered from all therapy-related toxicity to =< grade 2 (except alopecia, anemia
and any signs or symptoms of androgen deprivation therapy) at the time of registration

- Poor prognosis disease as defined by any of the following:

- PSA nadir >=4.0, or

- Gleason score 8-10, or

- Time from ADT initiation to CRPC of =< 16 months

- Hemoglobin >= 90 g/L

- Neutrophils >= 1.5 x 10^9 /L

- Platelets >= 100 x 10^9/L

- Aspartate aminotransferase (AST) < 1.5 x upper limit of normal (ULN)

- Alanine aminotransferase (ALT) < 1.5 x ULN

- Bilirubin =< 1.0 x ULN (exceptions for Gilbert's syndrome)

- Creatinine =< 1.5 x ULN

Exclusion Criteria:

- Prior therapy with cabazitaxel or to other drugs formulated with polysorbate 80

- Prior taxanes for CRPC

- Prior enzalutamide, abiraterone or ketoconazole

- Other condition, illness, psychiatric condition, or laboratory abnormality that may
increase the risk associated with administration of cabazitaxel, study participation,
or may interfere with the interpretation of study results and in the judgment of the
investigator would make the patient inappropriate for entry into this study

- Histologic evidence of small cell/neuroendocrine prostate cancer

- Patients with reproductive potential who do not agree to use accepted and effective
method of contraception during the study treatment period and up to 6 months after the
last administered dose; the definition of "effective method of contraception" will be
based on the investigator's judgment