E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic 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 activity of FK228 in patients with metastatic prostate cancer who have developed a rising PSA while undergoing hormonal therapy. Activity will be measured as the rate of disease control (complete response [CR], partial response [PR], or stable disease [SD] for at least 6 months). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this trial are: • To evaluate the rate of PSA decline by >/=50%; • To evaluate the percentage of PSA decline; • To evaluate the time to PSA progression; • To evaluate the time to objective disease progression; • To assess the tolerability and safety of FK228; • To evaluate the effect of therapy on disease-related symptoms (Memorial Pain Scale); • To evaluate the effect of the therapy on performance status; and • To evaluate the pharmacokinetics of FK228. • To evaluate the duration of objective disease response
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Males aged >/=18 years; Histologically or cytologically confirmed metastatic prostate cancer with documented prpgression on hormonal therapy (objective progressive disease [PD], new bone lesions, or stable soft tissue or bone lesions with PSA increase); 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); and Serum testosterone level of <50 ng/mL in patients without surgical castration Written informed consent to participate in the study. |
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E.4 | Principal 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; • Major surgery within 2 weeks of study entry; • Prior treatment with chemotherapy; • Patients with known cardiac abnormalities such as: Congenital long QT syndrome Corrected QT (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 . 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 definitions and/or ejection fraction <40% by multiple-gated acquisition (MUGA) scan or <50% by echocardiogram and/or magnetic resonance imaging (MRI) • Patients with a history of sustained ventricular tachycardia (VT), ventricular fibrillation (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 interval; • Concomitant use of medications that are inhibitors of the cytochrome P-450 isoenzyme CYP 3A4 • Concomitant use of drugs which may cause a prolongation of the QTc • 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 magnetic resonance imaging [MRI] scans are required only if brain metastasis is suspected clinically); • Inadequate bone marrow or other organ function
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E.5 End points |
E.5.1 | Primary end point(s) |
• The rate of objective disease control, 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) Secondary Endpoints • Rate of PSA decline by >/=50%; • Percentage of PSA decline; • Time to PSA progression; • Duration of objective disease response • Time to objective disease progression; • Rate of grade 3 and grade 4 non-hematological toxicity, adverse events, 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; • Change in pain score on the Memorial Pain Scale for symptomatic patients; • Change in performance status; and • Steady-state concentrations of FK228.
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 |