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

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.

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