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: Randomized phase II trial to study the effectiveness of docetaxel with or without oblimersen in treating patients who have hormone-refractory adenocarcinoma (cancer) of the prostate.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the prostate recurrent prostate cancer stage IV prostate cancer	Drug: docetaxel  Drug: oblimersen  Procedure: antisense therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Austria
      Kaiser Franz Josef Hospital, Vienna,  A-1100,  Austria; Recruiting
Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      Onze Lieve Vrouw Ziekenhuis Aalst, Aalst,  B-9300,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark; Recruiting
Israel
      Assaf Harofeh Medical Center, Zerifin,  70300,  Israel; Recruiting
Italy
      Ospedale S. Camillo-Forlanini, Rome,  00152,  Italy; Recruiting
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting

Study chairs or principal investigators

Cora N. Sternberg, MD, FACP,  Ospedale S. Camillo-Forlanini   

Study ID Numbers:  CDR0000367489; EORTC-30021; AVENTIS-AVE3139E/2501; NCT00085228
Record last reviewed:  January 2005
Last Updated:  February 4, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085228
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08