title: Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  To determine the clinical activity of OGX-011, an antisense inhibitor of clusterin, in combination with docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer.
  
  
  METHODS
  Patients were randomly assigned 1:1 to receive docetaxel/prednisone either with (arm A) or without (arm B) OGX-011 640 mg intravenously weekly. The primary end point was the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 50% from baseline, with the experimental therapy being considered of interest if the proportion of patients with a PSA decline was more than 60%. Secondary end points were objective response rate, progression-free survival (PFS), overall survival (OS), and changes in serum clusterin.
  
  
  RESULTS
  Eighty-two patients were accrued, 41 to each arm. OGX-011 adverse effects included rigors and fevers. After cycle 1, median serum clusterin decreased by 26% in arm A and increased by 0.9% in arm B (P < .001). PSA declined by ≥ 50% in 58% of patients in arm A and 54% in arm B. Partial response occurred in 19% and 25% of patients in arms A and B, respectively. Median PFS and OS times were 7.3 months (95% CI, 5.3 to 8.8 months) and 23.8 months (95% CI, 16.2 months to not reached), respectively, in arm A and 6.1 months (95% CI, 3.7 to 8.6 months) and 16.9 months (95% CI, 12.8 to 25.8 months), respectively, in arm B. Baseline factors associated with improved OS on exploratory multivariate analysis were an Eastern Cooperative Oncology Group performance status of 0 (hazard ratio [HR], 0.27; 95% CI, 0.14 to 0.51), presence of bone or lymph node metastases only (HR, 0.45; 95% CI, 0.25 to 0.79), and treatment assignment to OGX-011 (HR, 0.50; 95% CI, 0.29 to 0.87).
  
  
  CONCLUSIONS
  Treatment with OGX-011 and docetaxel was well tolerated with evidence of biologic effect and was associated with improved survival. Further evaluation is warranted.
authors: British Columbia Cancer Agency, Vancouver, British Columbia, Canada. kchi@bccancer.bc.ca
authors: Kim N
authors: KN
authors: Chi
authors: Sebastien J
authors: SJ
authors: Hotte
authors: Evan Y
authors: EY
authors: Yu
authors: Dongsheng
authors: D
authors: Tu
authors: Bernhard J
authors: BJ
authors: Eigl
authors: Ian
authors: I
authors: Tannock
authors: Fred
authors: F
authors: Saad
authors: Scott
authors: S
authors: North
authors: Jean
authors: J
authors: Powers
authors: Martin E
authors: ME
authors: Gleave
authors: Elizabeth A
authors: EA
authors: Eisenhauer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D051152:Clusterin / Q000097:blood / Q000235:genetics; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D018570:Risk Assessment; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage; D013873:Thionucleotides / Q000008:administration & dosage; D013997:Time Factors; D017211:Treatment Failure; D014861:Washington
chemical_list: C495242:CLU protein, human; D051152:Clusterin; C503781:OGX-011; D043823:Taxoids; D013873:Thionucleotides; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D011241:Prednisone