A Research Study for Patients With Prostate Cancer

The purpose of this study is to evaluate the activity of romidepsin (depsipeptide,FK228) in patients with metastatic prostate cancer who have developed a rising prostate specific antigen (PSA) while undergoing hormonal therapy.


Eligibility Criteria:
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.