Efficacy and Safety Study of Xyotax to Treat Prostate Cancer

The purpose of this study is to determine whether Xyotax, a conjugate of the taxane drug paclitaxel, is effective in the treatment of prostate cancer that is no longer responsive to hormone therapy.

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)