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.