Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer

This phase II trial is studying how well vorinostat works in treating patients with progressive metastatic prostate cancer. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES: I. To evaluate the efficacy of oral SAHA in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy, as measured by the proportion of patients not progressed at 6 months. SECONDARY OBJECTIVES: I. To evaluate the safety of oral SAHA in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy. II. To assess the objective response rate of oral SAHA in patients with measurable disease when present. III. To assess the rate of PSA decline of \>= 50%. IV. To assess progression free and median survival in patients with castrate metastatic prostate cancer who have progressed on one prior chemotherapy. V. To evaluate pre and post-treatment tumor biopsies when available for the presence of changes in the expression of AR and Hsp90 client proteins, Thioredoxin, Thioredoxin Binding Protein, HDAC 3 (class I), HDAC 7 (class II), EZH2 and p21 expression. VI. To determine the effects of oral SAHA on IL-6, soluble IL-6 receptor and soluble gp130 levels in the blood. VII. To determine the accumulation and biodistribution of 18FDHT and correlate these findings with standard FDG PET, radionuclide bone scan, CT and/or MRI scans, as well as 18FDHT pharmacokinetics and tumor tissue staining for androgen receptor (AR) and Hsp90 client proteins (this applies only to patients at MSKCC under a separate protocol #00-095). OUTLINE: This is a multicenter study. Patients receive oral vorinostat (SAHA) once daily on days 1-21. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) after 4 courses receive an additional 3 courses. All other patients may continue treatment in the absence of disease progression or unacceptable toxicity. Blood samples are taken on day 15 of course 1, day 1 of course 2, during the last week of course 4, and at completion of study treatment. Blood is examined for interleukin (IL)-6, IL-6 receptor, and gp130 levels. After completion of study treatment, patients are followed periodically for survival.