Hormone Therapy and OGX-011 Before Radical Prostatectomy in Treating Patients With Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as flutamide and buserelin may stop the adrenal glands from producing androgens. OGX-011 may help flutamide and buserelin kill more tumor cells by making tumor cells more sensitive to the drugs. Giving flutamide and buserelin with OGX-011 before surgery may shrink the tumor so it can be removed during surgery. PURPOSE: Phase I trial to study the effectiveness of combining hormone therapy with OGX-011 before radical prostatectomy in treating patients who have prostate cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and recommended phase II dose of OGX-011 (clusterin antisense oligonucleotide) when administered with neoadjuvant hormonal therapy before radical prostatectomy in patients with adenocarcinoma of the prostate. Determine the toxicity of this regimen in these patients. Determine the pharmacokinetics of OGX-011 when this regimen is administered in these patients.. Assess the effects of this regimen on pathologic complete response rates in these patients. Correlate plasma and/or prostate concentrations of OGX-011 with patient response or toxicity measures. OUTLINE: This is a dose-escalation study of OGX-011. Patients receive OGX-011 IV over 2 hours on days 1, 3, 5, 8, 15, 22, and 29; oral flutamide three times daily for 4 weeks; and buserelin subcutaneously on day 1. Cohorts of 3-6 patients (except for 1 patient at starting dose) receive escalating doses of OGX-011 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose is the dose preceding the MTD. Patients undergo radical prostatectomy and bilateral pelvic lymphadenectomy 1 week after the last dose of neoadjuvant therapy. Patients are followed at 7 days after surgery and then at 3 months. PROJECTED ACCRUAL: Approximately 25-33 patients will be accrued for this study.

Official Title
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A Phase I Study Of Combination Neoadjuvant Hormone Therapy And Weekly OGX-011 (Clusterin Antisense Oligonucleotide) Prior To Radical Prostatectomy In Patients With Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: buserelin
* Drug: custirsen sodium
* Drug: flutamide
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate High-risk, localized disease that is previously untreated Minimum of 2 positive biopsies Meets at least 1 of the following criteria: Stage T3 Serum PSA greater than 10 ng/mL Gleason score 7-10 Gleason score 6 and at least 3 positive biopsies Potential candidate for radical prostatectomy PATIENT CHARACTERISTICS: Age Over 18 Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic WBC at least 3,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10.0 g/dL Hepatic Bilirubin normal AST and ALT normal PTT normal INR normal Renal Creatinine normal Cardiovascular No significant cardiac dysfunction Other Fertile patients must use effective contraception No known hypersensitivity to oligonucleotides, luteinizing hormone-releasing hormone analogs, or anti-androgens No evidence of active uncontrolled infection No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer No other serious illness, psychiatric disorder, or medical condition that would preclude study compliance No history of a significant neurological disorder that would preclude informed consent No geographical condition that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for prostate cancer Endocrine therapy No prior hormonal therapy for prostate cancer Radiotherapy No prior radiotherapy for prostate cancer No concurrent radiotherapy Surgery Not specified Other No concurrent heparin or warfarin anticoagulation No other concurrent investigational therapy No other concurrent cytotoxic therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: buserelin|nan|
|Drug: custirsen sodium|nan|
|Drug: flutamide|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage III prostate cancer, stage II prostate cancer