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

Study Overview
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Brief Summary
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RATIONALE: GTI-2040 may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may help docetaxel kill more tumor cells by making them more sensitive to the drug. PURPOSE: This phase II trial is studying how well giving GTI-2040 together with docetaxel and prednisone works in treating patients with prostate cancer that has not responded to hormone therapy.

Detailed Description
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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.

Official Title
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A Phase II Study of GTI-2040 in Combination With Docetaxel and Prednisone in Hormone-Refractory Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: GTI-2040
* Drug: docetaxel
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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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

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: GTI-2040|nan|
|Drug: docetaxel|nan|
|Drug: prednisone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA response rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median survival |  |  | 
| 1-year survival |  |  | 
| Response rate and duration |  |  | 

 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