SB-715992 in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Docetaxel or Paclitaxel

Study Overview
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Brief Summary
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Drugs used in chemotherapy, such as SB-715992, work in different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well SB-715992 works in treating patients with metastatic prostate cancer that did not respond to docetaxel or paclitaxel

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the prostate-specific antigen response to SB-715992 in patients with hormone-refractory, androgen-independent metastatic prostate cancer that failed prior taxane-based chemotherapy. SECONDARY OBJECTIVES: I. Determine the median overall survival and median progression-free survival of patients treated with this drug. II. Determine the objective response rate (confirmed and unconfirmed, complete and partial response) in patients with measurable disease treated with this drug. III. Determine the qualitative and quantitative toxic effects of this drug in these patients. IV. Determine, preliminarily, the pharmacokinetics and mechanism of activity of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 1.3-2.7 months.

Official Title
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A Phase II Study of SB-715992 (NSC-727990, IND-70273) in Taxane-Resistant Androgen-Independent Metastatic Prostate Cancer

Conditions
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Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage IV Prostate Cancer

Intervention / Treatment
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* Drug: ispinesib
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate Metastatic disease (N1 and/or M1) Unresponsive or refractory to androgen-deprivation therapy Must have received one, and only one, prior taxane-containing (docetaxel or paclitaxel) chemotherapy regimen for metastatic disease that was discontinued due to disease progression, intolerance, or patient request Evidence of disease progression as defined by ≥ 1 of the following: Progression of measurable disease Progression of evaluable disease Rising prostate-specific antigen (PSA) At least 2 consecutive rises in PSA levels, each taken ≥ 7 days apart PSA ≥ 5 ng/mL Must have pre-study PSA > 5 ng/mL Measurable or evaluable disease Soft tissue disease that has been irradiated within the past 2 months is not considered measurable disease Soft tissue disease that has been irradiated ≥ 2 months prior to study entry is considered measurable disease provided the lesion progressed after radiation Surgical or medical castration required If luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin) or LHRH antagonists (abarelix) were used, then must continue use during study therapy No prior or concurrent brain metastases (treated or untreated) If clinical suspicion of brain metastases, must meet the following criteria: Brain CT scan or MRI negative for metastatic disease within the past 56 days No new symptoms since radiographic evaluation Performance status - Zubrod 0-2 Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Bilirubin normal SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN) Creatinine ≤ 1.5 times ULN Creatinine clearance ≥ 40 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Fertile patients must use effective contraception No peripheral neuropathy ≥ grade 2 No prior allergic reaction attributed to compounds of similar chemical or biological composition to SB-715992 No ongoing or active infection No psychiatric illness or social situation that would preclude study participation No other uncontrolled illness No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated stage I or II cancer in complete remission No colony-stimulating factors during the first course of study therapy No concurrent anticancer biologic therapy See Disease Characteristics At least 4 weeks since prior chemotherapy and recovered See Disease Characteristics At least 4 weeks since prior flutamide or ketoconazole At least 6 weeks since prior bicalutamide or nilutamide No concurrent anticancer hormonal therapy except LHRH agonist or antagonist for patients who have not undergone orchiectomy See Disease Characteristics At least 4 weeks since prior radiotherapy and recovered Prior samarium Sm 153 lexidronam pentasodium allowed No prior strontium chloride Sr 89 No prior radiotherapy to ≥ 30% of bone marrow No concurrent anticancer radiotherapy See Disease Characteristics At least 3 weeks since prior surgery and recovered At least 2 weeks since prior and no concurrent use of any of the following CYP3A4 inhibitors or inducers: Clarithromycin Erythromycin Troleandomycin Rifampin Rifabutin Rifapentine Itraconazole Ketoconazole Fluconazole (dose > 200 mg/day) Voriconazole Nefazodone Fluvoxamine Verapamil Diltiazem Grapefruit juice Bitter orange Phenytoin Carbamazepine Phenobarbital Oxcarbazepine Hypericum perforatum (St. John's wort) Modafinil At least 6 months since prior and no concurrent amiodarone No other investigational drugs for 4 weeks before, during, and for 2 weeks after study therapy No other concurrent anticancer cytotoxic therapy No other concurrent anticancer therapy No concurrent combination antiretroviral therapy for HIV-positive patients Concurrent enrollment on SWOG-9205 (central prostate cancer serum repository protocol) allowed

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (ispinesib)<br>Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: ispinesib<br>* Given IV<br>* Other names: SB-715992;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of PSA response |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From date of registration to date of death due to any cause, assessed up to 3 years | 
| Progression-free survival |  | From date of registration to date of first observation of progressive disease, symptomatic deterioration, or death due to any cause, assessed up to 3 years | 
| Probability of objective response |  | Up to 3 years |