GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer

OBJECTIVES:

Primary

• Determine the efficacy of GTI-2040, docetaxel, and prednisone, in terms of prostate-specific antigen (PSA) response rate, in patients with hormone-refractory prostate cancer.

Secondary

• Determine objective tumor response in patients treated with this regimen.
• Determine the median time to progression in patients treated with this regimen.
• Determine the safety and tolerability of this regimen in these patients.
• Determine the median duration of PSA response in patients treated with this regimen.
• Correlate baseline and post-treatment levels of ribonucleotide reductase activity in tumor biopsies and peripheral blood mononuclear cells and tumoral expression of c-myc, R2 subunit protein, and markers of cellular proliferation and apoptosis with clinical outcomes in patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive GTI-2040 IV continuously on days 1-14, docetaxel IV on day 3 of course 1 and on day 1 of subsequent courses, and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 3.6-9.5 months.

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Metastatic carcinoma of presumptive prostate origin

• Bony metastases AND a serum prostate-specific antigen (PSA) level > 20 ng/mL
• Disease progression after prior hormonal therapy as defined by rising PSA levels

• At least 2 consecutive rises in PSA over a reference value, with measurements taken at least 7 days apart
• Prior hormonal therapy must include either medical (luteinizing hormone-releasing hormone [LHRH] agonist) OR surgical (orchiectomy) castration

• Patients who received prior LHRH agonist must continue or re-start such therapy
• Castrate levels of testosterone < 50 ng/dL
• PSA ≥ 20 ng/mL
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 3,000/mm^3

Hepatic

• AST and ALT ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin normal
• PTT ≤ 1.25 times upper limit of control
• INR ≤ 1.3

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Fertile patients must use effective contraception
• No symptomatic peripheral neuropathy ≥ grade 2
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to GTI-2040 or other study agents
• No concurrent uncontrolled illness
• No active or ongoing infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic filgrastim (G-CSF) or epoetin alfa

Chemotherapy

• No prior chemotherapy except monotherapy with oral estramustine
• At least 4 weeks since prior estramustine and recovered

Endocrine therapy

• See Disease Characteristics
• At least 6 weeks since prior bicalutamide*
• At least 4 weeks since prior flutamide, nilutamide, or cyproterone*
• Concurrent steroids allowed NOTE: *Patients must have evidence of disease progression despite cessation of antiandrogen therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to > 25% of bone marrow
• No prior isotope therapy

Surgery

• See Disease Characteristics

Other

• No concurrent prophylactic antibiotics
• No concurrent anticoagulants

• Concurrent low-dose warfarin for prophylaxis of central line thrombosis allowed
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents or therapies