Efficacy and Safety Study of Xyotax to Treat Prostate Cancer

Prostate cancer is the second leading cause of cancer death in American men. Hormonal
ablation, in the form of medical or surgical castration, is the cornerstone of management
for metastatic prostate cancer; however, treatment options for a patient in whom androgen
ablation fails are limited. Docetaxel and paclitaxel, taxanes that are cell cycle specific,
play a major role in advanced hormone-refractory prostate cancer treatment. In preclinical
studies, Xyotax, a conjugate of paclitaxel with enhanced permeability and retention in tumor
tissue, has an improved therapeutic profile, with both decreased systemic drug-related
toxicities and enhanced efficacy. Xyotax as a single agent has been studied in a broad
variety of syngeneic and xenogeneic tumor models. Recognizing that taxanes are active in
prostate cancer and preclinical data reports activity with Xyotax in docetaxel and
paclitaxel resistant cell lines, there is significant rationale to develop this agent in
prostate cancer. Thus, a phase II study is needed to evaluate the antitumor activity in two
subsets of hormone refractory prostate cancer patients: those with no prior systemic and
those with one prior systemic therapy.

Inclusion Criteria:

- Progressing adenocarcinoma of the prostate having failed prior hormone therapy

- Free of serious co-morbidity

- Have a life expectancy of ≥ 24 weeks

- Maintaining castrate status (either surgically or hormonally)

Exclusion Criteria:

- Patients with central nervous system metastases, except those patients who have had
excision or radiotherapy and remain asymptomatic, off steroids and with no evidence
of disease as shown by MRI for at least 6 months

- Patients known to be HIV positive

- Patients with active autoimmune disease

- Patients involving concurrent anticancer drug therapy

- Patients with unstable medical condition, such as uncontrolled diabetes mellitus or
hypertension; active infections requiring systemic antibiotics, antivirals, or
antifungals; clinical evidence of cardiac or pulmonary dysfunction including, but not
limited to: unstable CHF, uncontrolled arrhythmias, unstable coagulation disorders,
or recent myocardial infarction (within 6 months)