Study of OGX-011 Given Prior to Radical Prostatectomy in Patients With Localized Prostate Cancer
Study of OGX-011 Given Prior to Radical Prostatectomy in Patients With Localized Prostate Cancer
The purpose of this trial is to assess the effects of combined therapy with androgen ablation
 and OGX-011 (an antisense to clusterin) given prior to radical prostatectomy on pathologic
 complete response rates in men with localized prostate cancer and high risk features.
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.

 Study Design

 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.

 Study Objectives

 Primary Objectives

 -  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.

 Secondary Objectives

 -  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
 radical prostatectomy.

 -  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

 Treatment Plan

 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.
Inclusion Criteria:

 1. Histologically confirmed adenocarcinoma of the prostate, previously untreated

 2. Males ≥ 18 years of age.

 3. Potential candidate for radical prostatectomy

 4. Any of the following (minimum of 2 positive biopsies):

 -  Clinical stage T3

 -  Serum PSA > 10 ng/ml

 -  Gleason score 7-10

 -  Gleason score 6 and > 3 positive biopsies

 5. ECOG performance status 0-1

 6. WBC ≥ 3.0 x 10^9/L

 7. Hemoglobin ≥ 100 g/L

 8. Platelets ≥ 100 x 10^9/L

 9. PTT, INR, AST, ALT, creatinine, total bilirubin within normal limits

 10. Patients must sign an informed consent that complies with US Regulations (US 21 Code
 of Federal Regulations [CFR]) and the International Conference on Harmonization (ICH)
 Guideline for Good Clinical Practice (GCP) prior to undergoing treatment.

 Exclusion Criteria:

 1. Prior hormone, radiation, or chemotherapy for prostate cancer

 2. Evidence of active infection

 3. Patients receiving therapeutic doses of warfarin or heparin

 4. Severe end organ disease

 5. Patients who otherwise would not be candidates for radical prostatectomy because of
 health or tumour factors

 6. Patients will be excluded if they had any prior malignancy unless the prior malignancy
 was diagnosed and definitively treated at least five years previously and there has
 never been any evidence of recurrence.

 7. Other serious illness, psychiatric, or medical condition that would not permit the
 patient to be managed according to the protocol.