E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory Prostate cancer
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 5.0 |
E.1.2 | Level | CTEP |
E.1.2 | Classification code | 10036920 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this trial is to evaluate the safety and tolerability of extended treatment with depsipeptide in patients who have at least demonstrated stable disease on a prior Gloucester-sponsored depsipeptide clinical trial, and in the opinion of their physician/investigator might benefit from continued treatment with depsipeptide. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this trial are: • To evaluate the effect of depsipeptide therapy on performance status; • To evaluate the time to objective disease progression.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Written informed consent/authorization; • Patient has completed 6 cycles of therapy in a prior Gloucester-sponsored depsipeptide clinical trial; • Patient has immediate past participation (not to exceed 21 days from Day 15 of cycle 6 in the previous study) in a prior Gloucester-sponsored depsipeptide clinical trial; • Patient has demonstrated stable disease, partial response or complete response as best overall response in their prior Gloucester-sponsored depsipeptide clinical trial and such response must be ongoing at the time of enrollment; • Patient must have serum potassium levels >4.0 mEq/L and serum magnesium levels >2.0 mg/dL; • Negative urine or serum pregnancy test on females of childbearing potential; • Sexually active females of child-bearing potential must be willing to practice reliable methods of birth control to prevent pregnancy after entering the trial; • Sexually active males must be willing to practice reliable methods of birth control after entering the trial.
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E.4 | Principal exclusion criteria |
• Patients with known cardiac abnormalities such as: • Congenital long QT syndrome ; • QTc interval >480 milliseconds; • Patients with any cardiac arrhythmia requiring anti-arrhythmic medication; • Patients who have a history of coronary artery disease (CAD) e.g., angina Canadian Class II-IV (see Appendix G). 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 who have had a myocardial infarction within 12 months of study entry; • 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 New York Heart Association (NYHA) Class II to IV 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; • Concomitant use of medications which may cause a prolongation of QT/QTc • Concomitant use of medications that are inhibitors of the cytochrome P-450 isoenzyme CYP 3A4 • Absolute neutrophil count (ANC) <1.5 X 109 cells/L; • Platelet count <75 X 109 cells/L; • Serum creatinine concentration >2 mg/dL or creatinine clearance <40 mL/min; • AST (aspartate aminotransferase) and alanine aminotransferase (ALT) >2.0 X ULN or >5 X ULN in presence of demonstrable liver metastasis; • Bilirubin concentration >1.25 X ULN or >2.0 X ULN in the presence of demonstrable liver metastases; • Serum potassium <4.0 mEq/L and serum magnesium <2.0 mg/dL; • Failure to recover of any drug-related non-hematological toxicity to grade 1 or less or to baseline values unless otherwise indicated; • Concomitant use of warfarin (due to a potential drug to drug interaction with depsipeptide). • Patient is pregnant or nursing; • Patient has been on a prior Gloucester-sponsored depsipeptide clinical trial, left the trial and then received alternative anti-neoplastic therapy.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Time to objective disease progression; • Rate of grade 3 and grade 4 non-hematological toxicity, AEs, clinical laboratory data, rate of grade 4 hematological toxicity, rate of neutropenic fever/sepsis, number of blood transfusions, ECG findings, frequency of cycles and administrations delayed as result of toxicity, and the frequency of cycles and administrations requiring dose modification because of toxicity; and • Change in performance status. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |