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

Inclusion Criteria

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