Inclusion Criteria:

- Histological or cytological diagnosis of adenocarcinoma of the prostate

- Metastatic disease on chest, abdominal, or pelvic CT scan and/or bone scan

- Previous first-line treatment for CRPC with a docetaxel-containing regimen

- Current progressive disease

- Increasing serum PSA level (for patients who progress based only on increasing serum
PSA level, a minimum starting value of 5.0 ng/mL is required)

- Baseline laboratory values as defined

- Willing to continue primary androgen suppression with gonadotropin-releasing hormone
(GnRH) analogues (unless treated with bilateral orchiectomy)

- Karnofsky score ≥70%

- At least 21 days have passed since completing radiotherapy

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

- At least 21 days have passed since major surgery

- Recovered from any docetaxel therapy-related neuropathy to ≤grade 1 at the time of
randomization

- 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 randomization

- Able to tolerate a starting dose of 25 mg/m² cabazitaxel

- Willing to not add, delete, or change current bisphosphonate or denosumab usage

- Able to tolerate oral prednisone at 10 mg per day

- Competent to provide written informed consent

Exclusion Criteria:

- Received any other cytotoxic chemotherapy beyond the first-line docetaxel-containing
regimen as treatment for prostate cancer

- Received prior radioisotope with strontium 89 or samarium 153

- Received any cycling, intermittent, or continuous hormonal treatment within 21 days
prior to randomization with the exception of the continuous GnRH analogues (prior
treatment with abiraterone or MDV3100 is allowed as long as 21 days have passed since
last dose)

- Participated in a prior Phase 3 clinical study evaluating custirsen regardless of
study arm assignment

- Requiring ongoing treatment during the study with medications known to be either
strong CYP3A inhibitors or strong CYP3A inducers

- History of or current documented brain metastasis or carcinomatous meningitis,
treated or untreated

- Current symptomatic cord compression requiring surgery or radiation therapy

- Active second malignancy (except non melanomatous skin or superficial bladder cancer)
defined in general as requiring anticancer therapy or at high risk of recurrence
during the study

- Uncontrolled medical condition or significant concurrent illness that in the opinion
of the Investigator would preclude protocol therapy

- Known severe hypersensitivity to taxanes or polysorbate 80-containing drugs

- Planned concomitant participation in another clinical trial of an experimental agent,
vaccine, or device