Inclusion Criteria

Inclusion Criteria

- Age ≥ 18 years on the date of consent.

- Histological or cytological diagnosis of adenocarcinoma of the prostate.

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

- Systemic chemotherapy indicated due to progression while on or after androgen
ablative therapy defined as:

1. Progressive measurable disease: at least a 20% increase in the sum of the
longest diameters of measurable lesions over the smallest sum observed -or- the
appearance of one or more new lesions as assessed by CT scan during hormone
ablation treatment. Measurable lesions are nodal or visceral soft-tissue lesions
with nodal lesions ≥ 20 mm in diameter or visceral/soft-tissue lesions ≥ 10 mm
in diameter (see Section 6.3.1.1 ).

OR

2. Bone Scan Progression: appearance of 2 or more new lesions on bone scan during
hormone ablation treatment.

OR

3. Increasing serum PSA level: Two consecutive increases in PSA levels documented
over a previous reference value obtained at least one week apart are required.
If the third PSA value is less than the second, an additional fourth test to
confirm a rising PSA is acceptable. A minimum starting value of 5.0 ng/mL is
required for study randomization.

- Baseline laboratory values as stated below:

1. Creatinine ≤ 1.5 x upper limit of normal (ULN).

2. Bilirubin ≤ 1.1 x ULN (unless elevated secondary to conditions such as Gilbert's
disease).

3. SGOT (AST) and SGPT (ALT) ≤ 1.5 x ULN.

4. Castrate serum testosterone level (< 50 ng/dL-or-< 1.7 nmol/L).

- Must be willing to continue primary androgen suppression with gonadotropin-releasing
hormone (GnRH) analogues (either agonists or antagonists) throughout the study,
unless treated with bilateral orchiectomy.

- Adequate bone marrow function defined at screening as ANC ≥ 1.5 x 10^9 cells /L and
platelet count ≥ 100 x 10^9 /L.

- Karnofsky score ≥ 70% (see Appendix 17.2).

- At least 28 days has 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 randomization.

- At least 4 weeks have passed since receiving any investigational agent at the time of
randomization.

- Has recovered from any other therapy-related toxicity to ≤ grade 2, (except alopecia,
anemia and any signs or symptoms of androgen deprivation therapy).

- Patient must be willing to not add, delete or change their current bisphosphonate or
denosumab usage throughout study treatment to assure that adverse event reporting is
not confounded by changing their bisphosphonate or denosumab usage (unless withdrawn
or changed as a result of bisphosphonate or denosumab associated toxicity).

- Patients receiving more than 10 mg of prednisone per day (or steroid equivalent) at
screening must be willing to have the dose reduced to 10 mg of prednisone per day for
at least 7 days prior to randomization and maintained throughout study treatment.

- Written informed consent must be obtained prior to any protocol-specific procedures
being performed.

Exclusion Criteria

- Received any other cytotoxic chemotherapy as treatment for prostate cancer.

- Received any cycling, intermittent or continuous hormonal treatment 28 days prior to
randomization with the exception of the continuous GnRH analogues required in
Inclusion Criteria #6.

- Participated in a prior clinical study evaluating custirsen.

- History of or current documented brain metastasis or carcinomatous meningitis,
treated or untreated. (Brain imaging for asymptomatic patients is not required.)

- Current symptomatic cord compression requiring surgery or radiation therapy. (Once
successfully treated and there has been no progression, patients are eligible for the
study.) -Active second malignancy (except non-melanomatous skin or superficial
bladder cancer) defined as requiring anticancer therapy or at high risk of recurrence
during the study.

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

- Uncontrolled medical conditions such as heart failure, myocardial infarction,
uncontrolled hypertension, stroke or treatment of a major active infection within 3
months of randomization, as well as any significant concurrent medical illness that
in the opinion of the Investigator would preclude protocol therapy.

- Planned concomitant participation in another clinical trial of an experimental agent,
vaccine, or device. Concomitant participation in observational studies is acceptable.