Ixabepilone in Treating Patients With Metastatic Prostate Cancer

Study Overview
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Brief Summary
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Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well ixabepilone works in treating patients with metastatic prostate cancer that has not responded to previous hormone therapy.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the effect on percent with a 50% decrease in PSA response in patients with metastatic prostate cancer who have progressed on androgen ablation therapy and are classified into 1 of 3 separate categories: Never received prior chemotherapy/cytotoxic therapy Received prior taxane-based regimen Received 2 prior cytotoxic chemotherapy regimens (including, but not limited to, prior taxane and anthracyclines) SECONDARY OBJECTIVES: I. Determine measurable disease response in patients with measurable disease treated with this drug and overall response rate. II. Determine the toxic effects of this drug in these patients. III. Determine the duration of PSA and measurable disease response in patients treated with this drug. IV. Determine the expression of p53, multidrug resistance protein, and Bcl-2 by immunohistochemistry in the primary tumors of patients treated with this drug. OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (none vs 1 prior taxane-containing regimen vs 2 prior cytotoxic regimens). Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Official Title
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Phase II Study of a Weekly Schedule of BMS-247550 for Patients With Hormone Refractory 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: ixabepilone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate Metastatic disease Evidence of disease progression (e.g., new lesions on bone scan or new/enlarging lesions on CT scan) OR rising prostate-specific antigen (PSA) within the past 4 weeks Radiologic evidence of hydronephrosis alone is not considered evidence of metastatic disease (e.g., increasing PSA) Patients with bone metastases only (i.e., lacking soft tissue disease) must have a PSA level >= 10 ng/mL within the past week Patients with stable disease and rising PSA must show 2 consecutive rises in PSA measurements taken at least 2 weeks apart Most recent PSA level must be obtained within the past 4 weeks Disease progression after prior anti-androgen withdrawal must be confirmed by a rising PSA after the 4-6 week washout period (e.g., PSA level higher than the last PSA obtained while on anti-androgen therapy) Failed prior bilateral orchiectomy or other primary hormonal therapy Patients who have not undergone bilateral orchiectomy must continue on luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g., abarelix) during study treatment AND must have a serum testosterone level =< 50 ng/dL within the past 4 weeks to confirm androgen suppression ECOG 0-2 Granulocyte count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 WBC >= 4,000/mm^3 SGPT =< 2 times upper limit of normal Bilirubin =< 1.5 mg/dL INR normal Creatinine =< 1.5 mg/dL Creatinine clearance >= 50 mL/min No New York Heart Association class III-IV heart disease No myocardial infarction within the past 6 months No active angina pectoris No evidence of ventricular dysrhythmias or other unstable arrhythmia Rate-controlled atrial fibrillation allowed provided the patient is asymptomatic No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer No serious medical illness or active infection that would preclude study participation No concurrent prophylactic filgrastim (G-CSF) No more than 2 prior cytotoxic chemotherapy regimens for hormone-refractory disease At least 4 weeks since prior chemotherapy with a taxane-based regimen, mixantrone, or another cytotoxic chemotherapy regimen provided there is evidence of progressive disease At least 4 weeks since prior flutamide AND continued evidence of progressive disease At least 6 weeks since prior bicalutamide or nilutamide AND continued evidence of progressive disease At least 4 weeks since prior estrogen or estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products which may contain phytoestrogens) At least 4 weeks since prior hormonal therapy, including megestrol, finasteride, ketoconazole, or systemic corticosteroids No concurrent estrogen or estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products which may contain phytoestrogens) More than 4 weeks since prior radiotherapy No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium No other prior radioisotope No concurrent radiotherapy for pain control No more than 1 prior experimental (non-cytotoxic) therapy AND evidence of progressive disease At least 4 weeks since prior experimental therapy Concurrent bisphosphonates (e.g., pamidronate or zoledronate) allowed provided treatment was initiated at least 4 weeks ago and there is evidence of progressive disease No other concurrent investigational agents No concurrent therapeutic warfarin Concurrent prophylactic or therapeutic doses of low molecular weight heparin allowed provided criterion for INR is met No carcinomatous meningitis or brain metastases Fertile patients must use effective contraception No peripheral neuropathy > grade 1

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: Arm I<br>Patients are stratified according to prior chemotherapy (none vs 1 prior taxane-containing regimen vs 2 prior cytotoxic regimens). Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: ixabepilone<br>* Given IV<br>* Other names: Ixempra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With PSA Response | PSA response is defined as a decline from baseline value by >=50%, or normalization of PSA (PSA < 0.2 ng/lm), confirmed by a second measurement >= 4 weeks later. The proportion of patients with PSA response was reported separately for 3 strata. Additional patients accrued to this study were not included in this analysis. | Every 4 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Measurable Disease Response (Best Overall Response) | Only patients with measurable disease were included in this analysis. The proportion of patients with measurable disease response (based on RECIST: Response Evaluation Criteria in Solid Tumors) was reported separately for 3 strata. Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR | Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry | 
| Duration of PSA Response | Duration of PSA response was defined as the time from the date of onset of PSA response until the date the criteria were met for PSA progression. Only patients with a PSA response were included in this analysis. The results were reported separately for 3 strata. | Every 4 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry | 
| Duration of Measurable Disease Response | Duration of measurable disease response was defined as the time from the date when measurement criteria were met for complete or partial response, whichever status was recorded first, until the first date that recurrent or progressive disease was objectively documented based on RECIST (Response Evaluation Criteria in Solid Tumors). Only patients with measurable disease response were included in this analysis. | Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry |