Ignite Creation Date:
2025-12-25 @ 5:00 AM
Ignite Modification Date:
2025-12-26 @ 4:00 AM
Study NCT ID:
NCT00138918
Status:
COMPLETED
Last Update Posted:
2017-03-03
First Post:
2005-08-26
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Study of OGX-011 Given Prior to Radical Prostatectomy in Patients With Localized Prostate Cancer
Sponsor:
University of British Columbia
Organization:
Study Overview
Official Title:
A Phase II Study of OGX-011 Given Prior to Radical Prostatectomy in Patients With Localized Prostate Cancer
Status:
COMPLETED
Status Verified Date:
2017-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
Detailed Description:
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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: