A Phase II Study of OGX-011 Given Prior to Radical Prostatectomy in Patients With Localized Prostate Cancer
Clusterin as an anti-apoptotic cytoprotective chaperone protein upregulated in an adaptive
cell survival manner that confers resistance to various cell death triggers, including
hormone-, radiation-, and chemotherapy. In pre-clinical models, inhibition of clusterin
expression using the second generation antisense OGX-011 can enhance cell death following
treatment with androgen ablation, radiotherapy, and chemotherapy. In phase I clinical
trials, OGX-011 has been well tolerated and a biologically effective dose has been
identified in humans.
This is an open-label, non-blinded, phase II clinical, tissue pharmacokinetic and
pharmacodynamic study of weekly OGX-011 and neoadjuvant hormone therapy prior to radical
prostatectomy in patients with localized prostate carcinoma and high-risk features.
- To assess the effects of combined neoadjuvant hormone therapy (NHT) and OGX-011 prior
to radical prostatectomy on pathologic complete response rates in men with high risk
localized prostate cancer.
- To quantify changes in clusterin expression in residual prostate cancer after treatment
with NHT and OGX-011.
- To measure levels of full length OGX-011 in prostate tissues after 3 months of NHT.
- To assess the safety and tolerability toxicity of 3 months of OGX-011 and NHT prior to
- To measure evidence of OGX-011's effect on clusterin expression in patient peripheral
blood mononuclear cells (PBMNC).
- To measure evidence of OGX-011's effect on patient clusterin serum levels.
- To assess the effects of combined NHT and OGX-011 on time to PSA nadir.
- To determine PSA recurrence rates after combined NHT and OGX-011.
Key Eligibility Criteria
1. Histologically confirmed adenocarcinoma of the prostate, previously untreated
2. Potential candidate for radical prostatectomy
3. Any one of the following criteria (minimum of 2 positive biopsies):
- Clinical stage T3
- Serum PSA > 10 ng/ml
- Gleason score 7-10
- Gleason score 6 and > 3 positive biopsies
4. ECOG performance status 0-1
5. WBC ≥ 3.0 x 10^9/L
6. Hemoglobin ≥ 100 g/L
7. Platelets ≥ 100 x 10^9/L
8. PTT, INR, AST, ALT, creatinine, total bilirubin within normal limits
Approximately 45 newly diagnosed, previously untreated patients with clinically localized,
high-risk prostate carcinoma will be entered into this trial. These patients will receive
neoadjuvant hormone therapy (buserelin 9.9 mg subcutaneously x 1 injection with flutamide
250 mg orally T.I.D. for the first 4 weeks only) for 12 weeks in combination with OGX-011 (a
2'MOE phosphorothioate clusterin antisense oligonucleotide) weekly on a 4 week cycle for 3
courses. For week one, cycle one only, OGX-011 will be given on Days 1, 3 and 5. OGX-011 is
given at a dose of 640 mg by intravenous infusion over 2 hours. Radical prostatectomy will
take place within 14 days of the last dose of OGX-011.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess the effects of combined neoadjuvant hormone therapy (NHT) and OGX-011 prior to radical prostatectomy on pathologic complete response rates in men with high risk localized prostate cancer
See Detailed Description, Treatment Plan
Dr. Kim Chi
University of British Columbia
Canada: Health Canada