Docetaxel With or Without Oblimersen in Treating Patients With Hormone-Refractory Adenocarcinoma (Cancer) of the Prostate

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of docetaxel by making tumor cells more sensitive to the drug. PURPOSE: This randomized phase II trial is studying how well giving docetaxel together with oblimersen works compared to docetaxel alone in treating patients with hormone-refractory adenocarcinoma (cancer) of the prostate.

Detailed Description
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OBJECTIVES: Primary Compare the activity of docetaxel with or without oblimersen, in terms of prostate-specific antigen response, in patients with hormone-refractory adenocarcinoma of the prostate. Compare the toxicity of these regimens in these patients. Secondary Compare the time to progression in patients treated with these regimens. Compare survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, metastatic disease (M0 vs M1 with non-measurable lesions only vs M1 with measurable lesions), prior estramustine (yes vs no), and prior bisphosphonates (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive docetaxel IV over 1 hour on day 5 and oblimersen IV continuously on days 1-7. Arm II: Patients receive docetaxel IV over 1 hour on day 1. In both arms, treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until progressive disease and then every 16 weeks thereafter. PROJECTED ACCRUAL: A total of 102 patients (51 per treatment arm) will be accrued for this study.

Official Title
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Randomized Phase II Trial of Docetaxel (Taxotere) and Oblimersen (Antisense Oligonucleotide Directed to BCL-2) Versus Taxotere Alone in Patients With Hormone-Refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: oblimersen sodium
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Hormone-refractory disease Disease progression after prior hormonal therapy with luteinizing hormone-releasing hormone (LH-RH) analogues or orchiectomy and antiandrogens (given together or consecutively) Prostate-specific antigen (PSA) progression documented by at least 2 increases in PSA values over previous PSA reference value Must demonstrate continued PSA elevation for at least 6 weeks after discontinuation of antiandrogen therapy PSA ≥ 5 ng/mL (Hybritech or equivalent) within the past week Testosterone ≤ 0.5 ng/mL* NOTE: *Patients with medical castration with LH-RH analogue must continue with LH-RH analogue throughout the study No evidence of painful and/or destructive bone metastases requiring concurrent radiotherapy, bisphosphonates, or bone-seeking radionuclides Other bone metastases allowed No clinical evidence of brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 WBC ≥ 3,500/mm^3 Hemoglobin ≥ 10 g/dL Hepatic AST and ALT ≤ 1.5 times upper limit of normal (ULN) Bilirubin ≤ ULN PTT and PT ≤ 1.5 times ULN OR INR ≤ 1.3 Renal Creatinine ≤ 1.5 times ULN OR Creatinine clearance ≥ 50 mL/min Cardiovascular No unstable angina No uncontrolled hypertension No deep venous thrombosis within the past 6 months No cerebrovascular accident, transient ischemic attack, or myocardial infarction within the past 6 months Pulmonary No pulmonary embolism No history of interstitial pneumonitis No history of pulmonary fibrosis Other Adequate venous access HIV negative No active infection No pre-existing neuropathy No hypersensitivity to phosphorothioates No hypersensitivity to oligonucleotides or any other component of the oblimersen formulation or to drugs formulated with polysorbate No psychological, familial, sociological, or geographical condition that would preclude study compliance No other malignancy within the past 5 years except adequately treated superficial urothelial or skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Prior estramustine allowed No other prior chemotherapy No concurrent estramustine Endocrine therapy See Disease Characteristics At least 6 weeks since prior flutamide, bicalutamide, or nilutamide More than 6 weeks since prior hormonal manipulation with PC-SPES Concurrent LH-RH agonist allowed No concurrent antiandrogens Radiotherapy See Disease Characteristics No prior radiotherapy involving > 25% of marrow-producing area No prior bone-seeking radionuclides No concurrent radiotherapy (including palliative therapy for painful bone metastases) No concurrent bone-seeking radionuclides Surgery See Disease Characteristics Other Prior bisphosphonates allowed No concurrent anticoagulation except for low-dose warfarin (1 mg/day) No concurrent regular (daily) intake of opioid analgesics No other concurrent experimental drugs or anticancer drugs No concurrent bisphosphonates

Ages Eligible for Study
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Minimum Age: 18 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: oblimersen sodium|nan|
|Drug: docetaxel|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate-specific antigen response as measured by Bubley criteria every course until progression or after 12 courses |  |  | 
| Severe toxic events as measured by CTCAE v3.0 every course until progression or after 12 courses |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression as measured by RECIST and Bubley criteria every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death |  |  | 
| Toxicity as measured by CTCAE v3.0 every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death |  |  | 
| Objective response as measured by RECIST every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death |  |  | 
| Overall survival as measured by Logrank every 3 courses, and then every 8 weeks until progression, and every 16 weeks from progression until death |  |  | 

 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