Table 1.

Clinical trials for advanced prostatic carcinoma using ncRNA therapeutics.

Trial Title	Therapeutic (Type) and MOA	Characteristics	Regimen	Major Outcomes
A Randomized Phase II Study of OGX-427 (a Second-Generation Antisense Oligonucleotide to Heat Shock Protein-27) in Patients with Castration-Resistant Prostate Cancer Who Have Not Previously Received Chemotherapy for Metastatic Disease. (NCT01120470)	Apatorsen/OGX-427 (a second-generation ASO) targets cytoprotective Hsp27. Downregulation of Hsp27 is expected to enhance sensitivity to cytotoxic agents.	74 patients were randomized to receive apatorsen + prednisone (n  =  36) or prednisone alone (n  =  38). The primary endpoint was disease progression at 12 weeks.	Three loading doses at 600 mg IV within the first 10 days of initiating treatment, followed by weekly doses of 1000 mg IV up to 12 weeks.	Apatorsen  +  prednisone produced a significant PSA decline but did not change the proportion of CRPC patients without disease progression at 12 weeks, compared with prednisone alone.
A Randomized Phase III Study Comparing Cabazitaxel/Prednisone in Combination with Custirsen (OGX-011) to Cabazitaxel/Prednisone for Second-Line Chemotherapy in Men with Metastatic Castrate-Resistant Prostate Cancer (AFFINITY) (NCT01578655)	Custirsen (ASO) downregulates Clusterin. Clusterin (a cytoprotective heat shock protein) regulates apoptosis and is upregulated by chemotherapy.	635 patients were randomized. Co-primary objectives were to evaluate overall survival (OS) in patients receiving Cbz/P/C (n = 317) versus Cbz/P (n = 318) alone.	21-day cycles of 25 mg/m2 IV Cbz on day 1 with 10 mg oral P daily with or without 640 mg IV of C on days 1, 8, and 15 (plus 3 prior loading doses) until disease progression, unacceptable toxicity, or 10 cycles obtained.	No significant survival benefits were demonstrated.
Randomized Phase II Trial of Docetaxel (Taxotere) and Oblimersen (Antisense Oligonucleotide Directed to BCL-2) versus Taxotere Alone in Patients with Hormone-Refractory Prostate Cancer (NCT00085228)	Oblimersen (ASO) selectively downregulates Bcl-2 (anti-apoptotic proto-oncogene) expression.	115 Chemotherapy naive patients were randomized to receive docetaxel + oblimersen (n = 58) or docetaxel (n = 57) alone. Biologic anti-tumor activity (based on PSA response: Bubley Criteria)	Docetaxel 75 mg/m2 on day 1 or oblimersen 7 mg/kg/day continuous IV infusion on days 1–7 with docetaxel 75 mg/m2 on day 5 every 3 weeks for ≤12 cycles. Patients in the docetaxel group received a median of eight cycles and those in the docetaxel + oblimersen group received a median of six cycles	The selected endpoint (reduction of PSA > 30%) was not achieved in any arm of the study, indicating that oblimersen was not beneficial in this selected cohort, but Bcl-2 expression was not analyzed.

MOA = mechanism of action, Cbz = cabazitaxel, P = prednisone, C = custirsen.