a research study for patients with prostate cancer

Conditions: Prostate Cancer; Metastases

Summary: 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.

Keywords: prostate cancer androgen independent metastatic prostate cancer patients with rising psa romidepsin