E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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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 |
To determine if orteronel plus prednisone improves Radiographic Progression-Free Survival (rPFS) To determine if orteronel plus prednisone improves Overall Survival (OS)
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E.2.2 | Secondary objectives of the trial |
To determine if orteronel plus prednisone improves 50% Prostate-Specific Antigen (PSA) response at 12 weeks To evaluate changes in Circulating Tumor Cell (CTC) counts To evaluate whether orteronel improves time to pain progression
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Two sub studies, bone biomarker and CTC biomarker profiling will be conducted at selected sites, however France will not be chosen for this part of the study. The objective of the bone biomarker sub study is to evaluate changes in markers of bone turnover, such as serum N-telopeptide and serum bone-specific alkalinephosphatase, in approximately 240 patients within the overall study population; and for the CTC biomarker profiling to assess candidate biomarkers predictive of orteronel antitumor activity including, but not limited to, the TMPRSS2:ERG fusion gene, the AR gene and the PTEN gene and the other clinical endpoints such as OS and time to disease progression. Details of these sub studies are provided in the protocol C21004, dated 21stJuly 2010. |
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E.3 | Principal inclusion criteria |
Each patient must meet all of the following inclusion criteria: •Voluntary written consent •Male patients 18 years or older •Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma •Radiograph-documented metastatic disease •Progressive disease •Prior surgical castration or concurrent use of an agent for medical castration •Either absence of pain or pain not requiring use of any opioid or narcotic analgesia in the 2 weeks prior to study entry •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 •Even if surgically sterilized, patients must Practice effective barrier contraception to one month after the last dose of study drug, OR Abstain from heterosexual intercourse •Meet screening laboratory values as specified in protocol •Stable medical condition
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E.4 | Principal exclusion criteria |
Patients meeting any of the following exclusion criteria are not to be enrolled in the study: •Known hypersensitivity to orteronel, prednisone or gonadotropin-releasing hormone (GnRH) analogue •Received prior therapy with orteronel, aminoglutethimide, ketoconazole or abiraterone •Received antiandrogen therapy within 6 weeks for bicalutamide and 4 weeks for all others prior to first dose of study drug •Continuous daily use of oral prednisone or oral dexamethasone for more than 14 days within 3 months prior to study •Received prior chemotherapy for prostate cancer •Exposure to radioisotope therapy within 4 weeks of receiving first dose of study drug; exposure to external beam radiation within 2 weeks of start of screening until receiving the first dose of study drug •Documented central nervous system metastases •Treatment with any investigational compound within 30 days prior ro first dose of study drug •Current spinal cord compression, bilateral hydronephrosis or current bladder neck outlet obstruction •Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected •Uncontrolled cardiovascular condition as specified in study protocol •Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C •Unwilling or unable to comply with protocol •Life-threatening illness unrelated to cancer •Uncontrolled nausea, vomiting or diarrhea •Known gastrointestinal disease or procedure that could interfere with oral absorption or tolerance of orteronel
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine if orteronel and prednisone improves radiographic progression-free survival (rPFS) To determine if orteronel plus prednisone improves overall survival (OS) |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 198 |
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 | Yes |
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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All patients will be followed for survival (long-term follow-up) after discontinuing the treatment/short-term follow-up portion of the study. Long-term follow-up will continue until death or termination of the study by the sponsor. |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |