900PD - A randomized phase II study of OGX-427 plus prednisone (P) vs. P alone in patients (pts) with metastatic castration resistant prostate cancer (CRPC)

Date 30 September 2012
Event ESMO Congress 2012
Session Genitourinary tumors, prostate
Topics Anticancer agents
Prostate Cancer
Therapy
Biological Therapy
Presenter Kim Chi
Authors K.N. Chi1, E.Y. Yu2, S. Ellard3, S.J. Hotte4, J.R. Gingerich5, A.M. Joshua6, M.E. Gleave7
  • 1Oncology, BC Cancer Agency - Vancouver Centre, V5Z4E6 - Vancouver/CA
  • 2Medical Oncology, University of Washington, Seattle/US
  • 3Medical Oncology, BC Cancer Agency - Centre for the Southern Interior, V1Y5L3 - Kelowna/CA
  • 4Medical Oncology, Juravinski Cancer Centre, Hamilton/CA
  • 5Medical Oncology, CancerCare Manitoba, Winnipeg/CA
  • 6Medical Oncology, Princess Margaret Hospital, Toronto/CA
  • 7Urological Sciences, University of British Columbia, Vancouver/CA

Abstract

Background

Heat Shock Protein 27 (Hsp27) is a multi-functional chaperone that regulates cell signaling and survival pathways implicated in cancer progression. In prostate cancer models, Hsp27 chaperones androgen receptor (AR) and enhances transactivation of AR-regulated genes. OGX-427 is a 2nd generation antisense that inhibits Hsp27 expression with in vitro and in vivo efficacy and was well tolerated in phase I studies.

Methods

Chemotherapy-naive pts with no/minimal symptoms were randomized to receive OGX-427 600 mg IV x 3 loading doses then 1000 mg IV weekly with 5 mg PO BID or P only. Primary endpoint was the proportion of pts progression free at 12 weeks (PCWG2 criteria). A 2-stage MinMax design (HO = 5%, HA > 20%, α = 0.1, � = 0.1) with 32 evaluable pts/arm provides 70% power to detect the difference at 0.10 (1-sided). Secondary endpoints include PSA decline, measurable disease response and circulating tumour cell (CTC) enumeration.

Results

64 pts have been randomized; results of pts in the first stage are presented here (42 pts: 22 on OGX-427 + P, 20 on P). 10 pts are too early to evaluate (4) or non-evaluable (6) for week 12 progression. Baseline median age was 7 years (53-89); ECOG PS 0/1 in 67/33% of pts; median PSA of 66 (6-606); metastases in bone/lymph nodes/liver or lung was 74/57/10%; 19% had prior P treatment; 93% had ≥5 CTC/7.5 ml. Adverse events (AEs) have been mainly grade 1/2 OGX-427 infusion reactions. 6 pts had 15 grade 3/4 AEs considered OGX-427 related. There were 3 grade 4 AEs: hemolytic uremic syndrome, pulmonary embolus and dizziness. At week 12, the proportion of pts progression free was 12/17 (71%) (95% CI: 0.440, 0.897) in OGX427 + P treated pts and 6/15 (40%) (95% CI: 0.163, 0.677) in pts on P. A ≥50% PSA decline occurred in 11/22 (50%) of pts on OGX-427 + P and 4/20 (20%) pts treated with P. Measurable disease response occurred in 4/9 (44%) pts on OGX-427 + P (1CR, 3PR) and 0/12 pts on P. CTC conversion from ≥5 to <5/7.5 ml occurred in 12/22 (55%) pts on OGX-427 + P and 7/17 (41%) treated with P.

Conclusions

These data provide clinical evidence for the role of Hsp27 as a therapeutic target in prostate cancer and support continued evaluation of OGX-427 for pts with CRPC.

Disclosure

M.E. Gleave: Chief Scientific Officer: OnncoGenex Technologies Inc. Stock ownership: Oncogenex Technologies Inc.

All other authors have declared no conflicts of interest.