Inclusion Criteria

1. Age ≥ 18 years on the date of consent.
2. Histological or cytological diagnosis of adenocarcinoma of the prostate.
3. Metastatic disease at screening on a chest, abdomen or pelvic CT or bone scan.
4. Concurrent pain and analgesic use that is viewed by the Investigator to be related to prostate cancer.
5. Received at least 4 cycles of prior docetaxel-based first-line chemotherapy for metastatic disease based on a q3 week schedule of docetaxel. Patients treated on a weekly or alternate schedule for first-line docetaxel must have received an accumulated dose of docetaxel of at least 300 mg/M2.
6. Current progressive disease during or after completing first-line docetaxel treatment.
7. Baseline laboratory values at screening visit within protocol defined limits.
8. Must be willing to continue primary androgen suppression with luteinizing hormone releasing hormone (LHRH) analogues throughout the study, if not treated with bilateral orchiectomy.
9. Adequate bone marrow function.
10. Karnofsky score ≥ 70% at screening visit.
11. At least 21 days have passed since completing radiotherapy at the time of randomization.
12. At least 21 days have passed since completing any cytotoxic agent or investigational agent given in combination with the docetaxel-based first-line therapy, including ASOs (except custirsen which is an exclusion criterion), at the time of randomization.
13. Has recovered from all therapy related toxicity to ≤ grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy).
14. Patient can tolerate a starting dose of docetaxel of 75 mg/M2 or cabazitaxel at 25 mg/M2.
15. Patient must have remained on the same bisphosphonate or denosumab usage for a minimum of 12 weeks prior to randomization.
16. Written informed consent must be obtained prior to any protocol-specific procedures being performed.

Exclusion Criteria

1. More than two interruptions in first-line docetaxel therapy. An interruption will be defined as more than 6 weeks between doses.
2. Life expectancy less than 12 weeks.
3. Previously participated in any clinical trial evaluating custirsen.
4. Received any other cytotoxic chemotherapy as a second-line treatment after first-line docetaxel-based therapy.
5. Not on any opioid analgesic regimen for their prostate cancer-related pain.
6. Receiving more than one drug within each of the separate categories of long-acting opioid, short-acting opioid, and non-opioid.
7. Receiving any analgesic specified in the protocol as unacceptable for this study.
8. Planned concomitant participation in another clinical trial of an experimental agent, vaccine or device. Concomitant participation in observational studies is acceptable.
9. Inability to communicate and read in English, Spanish or French.