A Research Study for Patients With Prostate Cancer

Inclusion Criteria: * Males ≥18 years; * Written informed consent/authorization; * Histological or cytological confirmation of metastatic prostate cancer with documented progression on hormonal therapy (objective progressive disease \[PD\], new bone lesions, or stable soft tissue or bone lesions with PSA increase); * Patients must have either measurable disease or bone metastasis. Patients with measurable disease are preferred; * Rising PSA, with a minimum study entry PSA of ≥5 ng/mL; * Karnofsky performance status of ≥80%; * Life expectancy of \>12 weeks; * For patients treated with anti-androgens, elevation of PSA must be demonstrated after cessation of anti-androgen treatment; * Three lines of hormonal therapy are permitted prior to study entry (anti-androgen withdrawal is not considered as a second hormonal treatment); * Serum testosterone level of \<50 ng/mL in patients without surgical castration; * Patients must have serum potassium levels \>4.0 mEq/L and serum magnesium levels \>2.0 mg/dL. Exclusion Criteria: * Concomitant use of any anti-cancer therapy, except for continued use of luteinizing hormone-releasing hormone (LHRH) agonists or antiandrogens, or bisphosphonates or steroids initiated at least 4 weeks prior to study entry; * Concomitant use of any investigational agent, including PC-SPES; * Use of any investigational agent within 4 weeks of study entry; * Concomitant use of warfarin (due to a potential drug-to-drug interaction with depsipeptide); * Major surgery within 2 weeks of study entry; * Prior treatment with chemotherapy; * Patients with known cardiac abnormalities such as: * Congenital long QT syndrome; * QTc interval \> 480 milliseconds; * Patients who have had a myocardial infarction within 12 months of study entry; * Patients who have a history of coronary artery disease (CAD) e.g., angina Canadian Class II IV (see Appendix K). In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present; * Patients with an ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥2 mm). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present; * Patients with congestive heart failure that meets NYHA Class II to IV (see Appendix J) definitions and/or ejection fraction \<40% by MUGA scan or \<50% by echocardiogram and/or magnetic resonance imaging (MRI); * Patients with a history of sustained VT, VF, Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD); * Patients with hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes (in doubt, see ejection fraction criteria above); * Patients with uncontrolled hypertension i.e., ≥160/95; * Patients with any cardiac arrhythmia requiring anti-arrhythmic medication; * Concomitant use of medications which may cause a prolongation of QT/QTc (see Appendix D) interval; * Concomitant use of medications that are inhibitors of the cytochrome P-450 isoenzyme CYP 3A4 (see Appendix E); * Clinically significant active infection; * Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; * Previous extensive radiotherapy involving 30% of bone marrow (e.g., whole of pelvis, half of spine); * Clinical or radiological imaging evidence of brain metastasis (computed tomography \[CT\] or MRI scans are required only if brain metastasis is suspected clinically); * Inadequate bone marrow or other organ function, as evidenced by: * hemoglobin \<9.0 g/dL (transfusions and/or erythropoietin are permitted); * absolute neutrophil count (ANC) ≤1.5 x 109 cells/L; * platelet count \<100 x 109 cells/L; * total bilirubin \>1.25 x upper limit of normal (ULN) for institution or \>2.0 x ULN in the presence of demonstrable liver metastases; * aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) \>2.0 x ULN or \>5.0 x ULN in the presence of demonstrable liver metastases; * serum creatinine \>2 mg/dL; * Serum potassium levels \< 4.0 mEq/L and serum magnesium levels \<2.0 mg/dL; * Coexistent second malignancy or history of prior malignancy within previous 5 years (excluding basal or squamous cell carcinoma of the skin that has been treated curatively); or * Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures.