Clinical trial NCT00106418: A Research Study for Patients With Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Metastases
Keywords: Prostate Cancer
Androgen independent metastatic prostate cancer patients with rising PSA
romidepsin
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2005-03-25
Enrollment: 35
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Rate of objective disease control
timeFrame: Up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Molife LR, Attard G, Fong PC, Karavasilis V, Reid AH, Patterson S, Riggs CE Jr, Higano C, Stadler WM, McCulloch W, Dearnaley D, Parker C, de Bono JS. Phase II, two-stage, single-arm trial of the histone deacetylase inhibitor (HDACi) romidepsin in metastatic castration-resistant prostate cancer (CRPC). Ann Oncol. 2010 Jan;21(1):109-13. doi: 10.1093/annonc/mdp270. Epub 2009 Jul 16.
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