E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with progressive castration-resistant prostate cancer previously treated with doxetaxel-based chemotherapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
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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 the benefit of MDV3100 as compared to placebo as assessed by overall survival. |
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E.2.2 | Secondary objectives of the trial |
• To determine the benefit of MDV3100 as compared to placebo as assessed by progression-free survival (PFS); • To determine the benefit of MDV3100 as compared to placebo as assessed by time to radiographic progression; • To determine the benefit of MDV3100 as compared to placebo as assessed by time to first skeletal related event; • To determine the benefit of MDV3100 as compared to placebo as assessed on quality of life; • To determine the benefit of MDV3100 as compared to placebo as assessed by time to prostate-specific antigen (PSA) progression; • To determine the benefit of MDV3100 as compared to placebo as assessed by pain palliation; • To determine the benefit of MDV3100 as compared to placebo as assessed by circulating tumor cell count (CTC) conversion rate; • To determine the safety of treatment with MDV3100 as compared to placebo; • To determine the effects of MDV3100 on electrocardiographic changes as compared to placebo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features; 2. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); 3. For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial; 4. Serum testosterone level < 1.7 nmol/L (50 ng/dL) at the Screening visit; 5. Patients receiving bisphosphonate therapy must have been on stable doses for at least four weeks; 6. Progressive disease by PSA or imaging after docetaxel-based chemotherapy in the setting of medical or surgical castration. Disease progression for study entry is defined as one or more of the following three criteria: • PSA progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the Screening visit should be ≥ 2 µg/L (2 ng/mL); • Soft tissue disease progression defined by RECIST 1.1 (Appendix A); • Bone disease progression defined by two or more new lesions on bone scan; 7. No more than two prior chemotherapy regimens with at least one regimen containing docetaxel; 8. ECOG performance status of 0–2; 9. Estimated life expectancy of ≥ 6 months; 10. Able to swallow the study drug and comply with study requirements; 11. Willing and able to give informed consent. |
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E.4 | Principal exclusion criteria |
1. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment; 2. Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed); 3. Absolute neutrophil count < 1,500/µL, platelet count < 100,000/µL, and hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit; (NOTE: patients may not have received any growth factors or blood transfusions within 7 days of the hematologic laboratory values obtained at the Screening visit); 4. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal at the Screening visit; 5. Creatinine > 177 µmol/L (2 mg/dL) at the Screening visit; 6. Albumin < 30 g/L (3.0 g/dL) at the Screening visit; 7. History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer; 8. Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide), 5-α reductase inhibitors (finasteride, dutasteride), estrogens, or chemotherapy within four weeks of enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments during the study; 9. Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or plans to initiate treatment with any of these treatments during the study; 10. Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within four weeks of enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments during the study; 11. History of prostate cancer progression on ketoconazole or plans to initiate ketoconazole treatment during the study; 12. Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) and radionuclide therapy within 8 weeks of enrollment (Day 1 visit); 13. Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery; 14. Structurally unstable bone lesions suggesting impending fracture; 15. History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack within 12 months of enrollment (Day 1 visit), or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization); 16. Clinically significant cardiovascular disease; 17. Have used or plan to use from 30 days prior to enrollment (Day 1 visit) through the end of the study medications known to lower the seizure threshold or prolong the QT interval; • Aminophylline/theophylline; • Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone); • Bupropion; • Class IA and III antiarrhythmics (e.g., amiodarone, bretylium, disopyramide, ibutilide, procainamide, quinidine, sotalol); • Dolasetron; • Droperidol; • Gatafloxacin/moxifloxacin; • Insulin; • Lithium; • Macrolide antibiotics (e.g., erythromycin, clarithromycin); • Pethidine; • Phenothiazine antipsychotics (e.g., chlorpromazine, mesoridazine, thioridazine); • Pimozide; • Tricyclic and tetracyclic antidepressants (e.g., amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine); • Venlafaxine. 18. Participation in a previous clinical trial of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or androgen receptor (e.g., BMS 641988) unless the patient had a PSA rise compared to his baseline level within the first 12 weeks of treatment with the investigational agent; 19. Participation in a previous clinical trial of MDV3100; 20. Use of an investigational agent within four weeks of enrollment (Day 1 visit) or plans to initiate treatment with an investigational agent during the study; 21. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months); 22. Major surgery within four weeks prior to enrollment (Day 1 visit). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy outcome is a comparison of overall survival between the MDV3100-treated and the placebo groups. |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
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) | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 MUST be followed for survival until death by means of a telephone contact every 12 weeks following their last study visit to confirm that the patients are alive and to document if they have received any additional antineoplastic therapy for their prostate cancer, and if they have had a skeletal-related event. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |