| Inclusion Criteria: | 1) Histologically confirmed adenocarcinoma of the prostate.
2) Progressive metastatic prostate cancer (positive bone scan or measurable disease) despite castrate levels of testosterone (either from orchiectomy or LHRH agonist therapy).
3) Patients may have either non-measurable disease OR measurable disease.
4) All patients must have a PSA >/= 2 ng/mL.
5) Progressive disease (PD) based on any one of the following: transaxial imaging, a rise in PSA, or radionuclide bone scan. Patients whose sole manifestation of PD is a rise in disease-related symptoms are not eligible. a)Measurable disease: PD is defined by the RECIST criteria. b)No measurable disease: a positive bone scan and elevated PSA is required. PSA evidence for PD prostate cancer during or after first-line chemotherapy consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least 1 weeks apart. c)Radionuclide bone scan: new metastatic lesions
6) Pts must have received at least 3 cycles of paclitaxel- or docetaxel-based therapy, with PD documented during therapy or following cessation. Pts may not have received more than 1 prior chemo regimen. a)Pts who required changes in their prior chemo regimen (addition of other agents) for PD will be considered to have had 2 prior chemo regimens and are not eligible. b)Pts who have been re-treated with the same taxane-based regimen are eligible provided other criteria are met. c)Pts will be excluded if they have previously received mitoxantrone, BMS-247550 (ixabepilone), or other epothilones.
7) Testosterone < 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy.
8) (ECOG) Performance Status 0 – 2.
9) Required Laboratory values: a) Creatinine </= 1.5 x upper limits of normal (ULN). If Cr. > 1.5 x ULN, then calculated creatinine clearance > 40cc/min. b) ALT and AST < 2.5 x ULN c) Granulocytes >/= 2,000/mm^3 d) Platelets >/= 100,000/ mm^3 e) Total bilirubin < 1.5 x ULN
10) Ejection fraction by MUGA scan or echocardiogram >/= lower limit of institutional normal. Patients with significant cardiovascular disease including congestive heart failure (NYHA class III or IV), active angina pectoris or recent (within 6 months) myocardial infarction are excluded.
11) Patients receiving hormonal therapy (i.e. any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES)) other than LHRH agonist or a stable dose of corticosteroid from a prior chemotherapy regimen must discontinue the agent for at least 4 weeks prior to enrollment. Progressive disease must be documented after discontinuation of the hormonal therapy.
12) No other systemic therapies for prostate cancer within 28 days prior to initiation of this protocol.
13) Prior radiation therapy completed >/= 4 weeks prior to enrollment
14) No radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment.
15) Men and members of all ethnic groups are eligible for this trial.
16) Age >/= 18 years |