A Research Study for Patients With Prostate Cancer

Study Overview
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Brief Summary
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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.

Official Title
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An Exploratory Phase II, Multicenter, Open-label Trial Evaluating the Activity and Tolerability of FK228 in Androgen Independent Metastatic Prostate Cancer Patients With Rising PSA

Conditions
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Prostate Cancer, Metastases

Intervention / Treatment
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* Drug: Romidepsin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romidepsin<br>13 mg/m^2 of romidepsin intravenously over 4 hours on Days 1, 8, and 15 of each 28-day cycle. | Drug: Romidepsin<br>* 13 mg/m2 of romidepsin intravenously over 4 hours on Days 1, 8, and 15 of each 28-day cycle.<br>* Other names: FK 228;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of objective disease control | Rate of objective disease control was defined as the proportion of patients with confirmed CR, PR, or SD for at least 6 months, as determined by the Response Evaluation Criteria for Solid Tumors (RECIST). | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Androgen independent metastatic prostate cancer patients with rising PSA, romidepsin