Docetaxel and Prednisone With/Out OGX-011 in Recurrent or Metastatic Prostate Cancer That Did Not Respond to Previous Hormone Therapy

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. OGX-011 may help docetaxel and prednisone kill more tumor cells by making tumor cells less resistant to the drugs. PURPOSE: This randomized phase II trial is studying how well giving docetaxel and prednisone with or without OGX-011 works in treating patients with recurrent or metastatic prostate cancer that did not respond to previous hormone therapy.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy, in terms of prostate-specific antigen response, of docetaxel and prednisone with or without OGX-011 in patients with hormone-refractory locally recurrent or metastatic prostate cancer. Secondary Determine the objective response rate and duration in patients treated with these regimens. Determine the safety and toxic effects of these regimens in these patients. Determine the overall and progression-free survival of patients treated with these regimens. OUTLINE: This is a multicenter, randomized, open-label study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive a loading dose of OGX-011 IV over 2 hours on days -7, -5, and -3. Patients then receive OGX-011 IV over 2 hours on days 1, 8, and 15, docetaxel IV over 1 hour on day 1, and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive docetaxel IV over 1 hour on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Official Title
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A Randomized Phase II Study of OGX-011 in Combination With Docetaxel and Prednisone or Docetaxel and Prednisone Alone in Patients With Metastatic Hormone Refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: custirsen sodium
* Drug: docetaxel
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the prostate Metastatic or locally recurrent disease Not curable with standard therapy Systemic chemotherapy is indicated, due to disease progression while receiving androgen-ablative therapy (i.e., hormone-refractory disease) Disease progression is defined as development of new metastatic lesions OR ≥ 2 consecutive rises in prostate-specific antigen (PSA) over a reference value Androgen ablative therapy must have included either medical or surgical castration Castrate level of testosterone (≤ 1.7 nmol/L) required if treated with medical androgen ablation Patients with documented disease progression while on peripheral antiandrogens must also have documented PSA progression after stopping antiandrogens PSA ≥ 5 ng/mL No known CNS metastases PATIENT CHARACTERISTICS: Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No known bleeding disorder Hepatic PT and PTT or INR normal Bilirubin normal AST and ALT ≤ 1.5 times upper limit of normal (ULN) Renal Creatinine ≤ 1.5 times ULN Cardiovascular No significant cardiac dysfunction Other Fertile patients must use effective contraception No pre-existing peripheral neuropathy ≥ grade 2 No active, uncontrolled infection No significant neurological disorder that would preclude study compliance No history of other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Chemotherapy No prior chemotherapy except estramustine and recovered No other concurrent chemotherapy Endocrine therapy See Disease Characteristics At least 4 weeks since prior antiandrogens (6 weeks for bicalutamide) Luteinizing hormone-releasing hormone (LHRH) agonist therapy must be continued* or restarted* during study treatment to maintain castrate levels of testosterone NOTE: *For patients receiving LHRH agonist therapy prior to study entry Radiotherapy At least 4 weeks since prior external beam radiotherapy except low-dose, nonmyelosuppressive radiotherapy Must have had less than 25% of marrow irradiated No prior strontium chloride Sr 89 No concurrent radiotherapy except low-dose, nonmyelosuppressive, palliative radiotherapy Surgery At least 2 weeks since prior major surgery Other At least 4 weeks since prior investigational agent At least 4 weeks since prior anticancer therapy No concurrent therapeutic anticoagulants except low-dose oral anticoagulants (i.e., 1 mg warfarin) or low molecular weight heparin No other concurrent investigational agents 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: OGX011, Docetaxel and Prednisone<br> | Drug: custirsen sodium<br>* 640mg IV for 2 hours - Cycle 1: Days -7, -5, -3, 1, 8, 15 (4 week cycle) Subsequent cycles: weekly on days 1, 8, 15 (3 week cycles)<br>Drug: docetaxel<br>* 75mg/m2 IV for 1 hour - Day 1 every 3 weeks (3 week cycles)<br>Drug: prednisone<br>* 5mg PO BID<br>|
| Active Comparator: Docetaxel plus prednisone<br> | Drug: docetaxel<br>* 75mg/m2 IV for 1 hour - Day 1 every 3 weeks (3 week cycles)<br>Drug: prednisone<br>* 5mg PO BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate-specific antigen (PSA) response measured by Bubley criteria at completion of study |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 2 years | 
| Time to treatment failure |  | 2 years | 

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