The purpose of this research study is to determine the safety and effectiveness of the
investigational drug, Ixabepilone, in men with high risk prostate cancer who plan to receive
Prostate cancer is a common and important health issue facing men in the United States. Most
patients with prostate cancer are identified when the disease is limited to the prostate
gland itself (localized prostate cancer). A standard treatment for some patients with
localized prostate cancer is removal of the prostate gland in an operation known as a
"radical prostatectomy." A sub-set of patients with localized prostate cancer can be
identified who are at high-risk of suffering a recurrence of prostate cancer after radical
prostatectomy. For these patients, additional treatments are being investigated to combine
with surgery in the hopes of increasing the chances for cure.
Several kinds of chemotherapy medicines have been used for advanced prostate cancer which
returns after initial therapy. Epothilones are a newly developed class of chemotherapy drugs
that appear promising for the treatment of many forms of cancer. Ixabepilone is drug in the
epothilone class of chemotherapy medicines that has shown encouraging results for the
treatment of advanced prostate cancer and other cancers in clinical trials.
This trial will include men with high-risk localized prostate cancer who will receive
treatment with ixabepilone (4 cycles over 12 weeks) prior to radical prostatectomy. The goal
of this trial will be to determine if analysis of genes and proteins in prostate cancer
tissue taken before and after treatment can be used to predict ixabepilone response. In
addition, this trial will evaluate the safety and feasibility of administering ixabepilone
prior to radical prostatectomy for patients at high-risk of developing recurrent prostate
The study has three phases: Screening, Treatment and Follow-up
- Screening: Eligibility will be verified
- Treatment: Subjects will receive Ixabepilone, which will be administered every 21 days
for 4 cycles prior to surgery
- Follow up: Subjects will be followed every 6 months for up to 5 years.
In addition, tissue will be collected at the time of surgery for genetic and protein
studies. Blood will also be collected pre and post therapy for proteomic and/or genetic
- Histologically-confirmed localized prostate cancer
- Predicted probability of recurrence >/= 30% as defined by the updated Kattan nomogram
- Pathologic material available for gene expression analysis including cancer present
in 2 or more cores and availability of unstained slides or formalin-fixed paraffin
embedded tissue blocks.
- No prior prostate cancer therapy (including hormonal, chemotherapy, radiation or
- Subjects must be considered as candidates for radical prostatectomy
- EGOG status
- Men of child-bearing potential are required to use an effective means of
- Required Initial Laboratory Values:
- ANC >/= 1500/uL
- Platelet Count >/= 100000/uL
- Creatinine Bilirubin AST < 2.5 X ULN
- ALT < 2.5 X ULN
- Hemoglobin >/= 9.0 g/dL
- A history of significant ventricular arrhythmias
- Neuropathy (> grade 1)
- Recent (within 6 months) myocardial infarction, congestive heart failure, transient
ischemic attack or stroke
- Active angina, including active stable and unstable angina
- Acute deep venous thrombosis and/or pulmonary embolism in the past 6 months
- Any prior hormonal therapy including the use of PC Spes or estrogen containing
- Other co-existing malignancies or malignancies diagnosed within the last 5 years,
with the exception of basal cell carcinoma.
- Patients with malignancy diagnosed more than 5 years ago and are disease free for at
least 5 years are not excluded.
- Recent (within 4 weeks) surgery or incomplete healing from surgery
- Known history of hypersensitivity reaction to a drug formulated in Cremophor EL
- Treatment with a non-approved or investigational drug within 30 days before Day 1 of
- Active infection requiring antibiotic therapy, or serious intercurrent illness.
- Any other major illness that in the investigators judgment will substantially
increase the risk associated with the subject's participation in this study.
- Unwillingness or inability to comply with procedures required in this protocol.