Ixabepilone With or Without Estramustine in Treating Patients With Progressive Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as ixabepilone and estramustine, use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether BMS-247550 is more effective with or without estramustine in treating prostate cancer. PURPOSE: This randomized phase I/II trial is studying the best dose of ixabepilone when given together with estramustine and to see how well giving ixabepilone together with estramustine works compared to ixabepilone alone in treating patients with progressive prostate cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of ixabepilone combined with estramustine in patients with progressive androgen-independent adenocarcinoma of the prostate. (Phase I) Compare the safety and efficacy of ixabepilone with or without estramustine in this patient population. (Phase II) Correlate the clinical outcomes with reverse transcriptase-polymerase chain reaction-based assay for prostate-specific antigen mRNA in patients treated with these regimens. OUTLINE: This is a dose-escalation study of ixabepilone (phase I) followed by a randomized, multicenter study (phase II). Phase I: Patients receive ixabepilone IV over 3 hours on day 2 and oral estramustine 3 times daily on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ixabepilone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Phase II: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive ixabepilone IV over 3 hours at the MTD on day 2 and estramustine as in phase I. Arm II: Patients receive ixabepilone IV over 3 hours at the MTD on day 1. Treatment in both arms repeats as in phase I. Patients are followed every 12 weeks until disease progression. PROJECTED ACCRUAL: A total of 3-12 patients will be accrued for phase I of this study and a total of 44-92 patients (22-46 per treatment arm) will be accrued for phase II of this study within 12-18 months.

Official Title
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A Phase I And Randomized Phase 2 Trial Of Epothilone B Analogue BMS 247550 (NSC # 710428) Administered Every 21 Days With Or Without Oral Estramustine Phosphate In Patients With Androgen Independent Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: estramustine phosphate sodium
* Drug: ixabepilone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the prostate Must have disease progression meeting 1 of the following criteria: Rising prostate-specific antigen (PSA) on at least 3 consecutive measurements taken more than 1 week apart Measurable disease, defined as new or progressive soft tissue masses on CT scan or MRI New metastatic lesions by radionuclide bone scan The most recent PSA must be at least 4 ng/mL if no measurable disease is present Ineligible if sole manifestation of progressive disease is an increase in disease-related symptoms Serum testosterone no greater than 50 ng/mL One of the following therapies for maintenance of castrate status required: Must continue on gonadotropin-releasing hormone analogs (e.g., leuprolide or goserelin) to maintain castrate levels of serum testosterone Developed disease progression after discontinuation of the antiandrogen that was part of the first-line hormonal therapy Prior surgical orchiectomy Developed disease progression after discontinuation of megestrol No known brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 No history of bleeding disorder that would preclude anticoagulation with warfarin Hepatic: Bilirubin normal AST/ALT no greater than 2.5 times upper limit of normal (ULN) PT/PTT normal (unless anticoagulated for other reasons [e.g., atrial fibrillation]) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No significant cardiovascular disease No symptomatic congestive heart failure No New York Heart Association class III or IV heart disease No active unstable angina pectoris No cardiac arrhythmia No myocardial infarction within the past 6 months No history of hemorrhagic or thrombotic cerebrovascular accident or deep venous thrombosis within the past 6 months Pulmonary: No pulmonary embolism within the past 6 months Other: Fertile patients must use effective contraception No history of allergic reactions to compounds of similar chemical or biological composition to the epothilones No history of recent gastrointestinal bleeding that would preclude anticoagulation with warfarin No other concurrent active malignancy except nonmelanomatous skin cancer Disease not considered currently active if completely treated with less than a 30% risk for relapse No other concurrent uncontrolled illness No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF) except for neutropenic fever No concurrent immunotherapy Chemotherapy: No prior chemotherapy No other concurrent chemotherapy Endocrine therapy: See Disease Characteristics Radiotherapy: No prior palliative radiotherapy to more than 25% of bone marrow No prior radioisotope therapy with strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium No concurrent therapeutic radiotherapy Concurrent focal radiotherapy for palliation of bone disease-related symptoms allowed at the investigator's discretion Surgery: See Disease Characteristics At least 4 weeks since prior major surgery Other: No other concurrent anticancer investigational or commercial agents or therapies No concurrent herbal, alternative, or food supplements (e.g., PC-SPES, saw palmetto, or St. John's Wort) No concurrent combination antiretroviral therapy for HIV-positive patients No initiation of bisphosphonates immediately before or during study Concurrent bisphosphonates allowed if developed disease progression while on stable doses Concurrent daily multivitamin 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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: estramustine phosphate sodium|nan|
|Drug: ixabepilone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer