E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Androgen-independent metastatic prostate cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10038359 |
E.1.2 | Term | Renal and urinary disorders |
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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 study is to compare the objective response rate of enzastaurin given in combination with docetaxel and prednisone followed by enzastaurin maintenance therapy in patients with HRPC during first-line therapy versus placebo plus docetaxel and prednisone followed by placebo as maintenance. An objective response rate is assessed via objective lesion response and a 50% decline from baseline in PSA. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are the following: to assess rate of 3-month PSA level decline of at least 30% in both treatment arms; to assess PSA velocity at 2 and 3 months in both treatment arms; to assess the following efficacy variables in both treatment arms (progression-free survival (PFS) time, overall survival (OS), and duration of response for responding patients); to assess the safety and adverse event profile in both treatment arms; to assess biomarkers relevant to enzastaurin and the disease state, as well as their correlation to clinical outcome; to characterize the pharmacokinetics (PK) of enzastaurin using intensive sampling in Part 1 (safety lead-in) and a sparse sampling strategy in randomized Part 2 of the trial; and to determine if PK of docetaxel is altered when administered in combination with enzastaurin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Pathologically confirmed diagnosis of adenocarcinoma of the prostate - Must have evidence of androgen-independent metastatic prostate cancer (documented bone or soft tissue metastases by bone scans, computed tomography [CT] scans, or Magnetic Resonance Imaging [MRI]) with evidence of progression defined as:(A) PSA progression; (B) Clinical and/or radiographic progression. - Must have had either an orchiectomy or have castrate level of testosterone (<50 ng/dL) maintained by luteinizing hormone-releasing hormone (LHRH) agonist - Prior intravenous radioisotopes (for example, samarium) must have been completed at least 6 weeks prior to enrollment - No prior chemotherapy for advanced prostate cancer - Have ECOG performance status of 0, 1, or 2 - Have adequate organ function - Reproductive potential must be either terminated or attenuated by the use of an approved contraceptive method (for example, condom) during and for 3 months following the study. - Disease-free of prior malignancies for >5 years with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or stage Ta transitional cell carcinoma of the bladder |
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E.4 | Principal exclusion criteria |
- Pretreated with any cytotoxic regimen for advanced prostate cancer and prior chemotherapy for any indication within 2 years of study entry - Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry - Receive concurrent administration of any other systemic anticancer therapy except LHRH agonist - Are unable to discontinue the use of carbamazepine, phenobarbital, phenytoin, or natural herbal medications (for example, PC-SPES, Saw Palmetto, St. John`s Wort) at least 14 days prior to enrollment - Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or severe heart disease, as defined by the New York Heart Association Class III or IV |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point of this study is to compare the objective response rate of enzastaurin given in combination with docetaxel and prednisone followed by enzastaurin maintenance therapy versus placebo plus docetaxel and prednisone followed by placebo as maintenance. |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | No |
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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Termine del mantenimento per tutti i pazienti in studio e prima visita di follow up a 30 giorni.I pazienti discontinuati dal trattamento verranno seguiti sino a 3 anni dall`ultima chemioterapia |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 8 |