A randomized phase II study of OGX-011 in combination with docetaxel and prednisone or docetaxel and prednisone alone in patients with metastatic hormone refractory prostate cancer (HRPC)

5069 Background: Clusterin, a cytoprotective chaperone protein that promotes cell survival, is associated with androgen independent progression and overexpressed in HRPC. OGX-011 (OGX, developed by OncoGenex Technologies/Isis Pharmaceuticals) is a 2’- methoxyethyl modified phosphorothioate antisense that inhibits clusterin expression in humans at doses of ≤640 mg and potentiates chemotherapy activity in prostate xenografts. The objective of this study was to determine the anti-tumor activity of OGX in combination with docetaxel (DOC) in patients (pts) with HRPC. Methods: Chemo-naive pts with metastatic HRPC were randomized to receive DOC 75mg/m 2 q3 weeks + OGX 640mg weekly as a 2-hour IV infusion (Arm A) + prednisone or DOC + prednisone (Arm B). Serum levels of clusterin were assessed serially. A single stage randomized phase II design was employed with PSA response rate (RR) as the primary endpoint (Bubley et al, J Clin Oncol 1999;17:3461). Planned sample size was 40 per arm: Arm A the hypotheses (H0:PSA RR<40% vs. H1:PSA RR>60%) could be tested at 10% β and 10% a, Arm B the true PSA RR could be estimated with half-width of the 90% confidence interval <13% if observed PSA RR was 40%. Results: 82 pts (41/arm) were enrolled from September 2005 to December 2006 at 12 centers. Baseline characteristics are similar in both arms (available to date for 63 pts): median age 67 (range: 49–84), PSA 110 μg/L (5.6–1261), hemoglobin 128 g/L (96–158), alkaline phosphatase 133 U/L (47–1294), LDH 193 U/L (120–741). ECOG performance status was 0 in 49% and 1 in 51%; 67% had bone/nodal disease only and 33% had other metastatic sites. To date, 56 pts have received ≥2 cycles. Toxicity due to OGX included grade 1/2 fevers and rigors in 37% and 67% pts respectively, but other adverse events were similar in both arms. PSA response has occurred in 43%, progression in 9%, and 48% have not yet met criteria for response or progression. Conclusions: Combined docetaxel and OGX is well tolerated in pts with metastatic HRPC and PSA responses have been observed. Pt treatment, follow-up and analysis of serum clusterin levels continue. Results by arm will be available by June 2007. Supported by a grant from the NCI-Canada/Canadian Cancer Society. No significant financial relationships to disclose.