E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Medical condition: metastatic castration-resistant prostate cancer (mCRPC) |
|
E.1.1.1 | Medical condition in easily understood language |
Medical condition: cancer of the prostate (a gland of the male reproductive system) which is metastatic (has spread to other parts of the body) and failed surgery and other treatment |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 study objective is to evaluate the seizure rate and monitor the safety of enzalutamide treatment in subjects with metastatic castration-resistant prostate cancer known to have risk factor(s) for seizure. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations (e.g., Health Insurance Portability Accountability Act (HIPAA) authorization for United States sites) must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable). 2. Subject has histologically confirmed metastatic adenocarcinoma of the prostate. 3. Subject has ongoing androgen deprivation therapy with a GnRH analogue (agonist or antagonist) or bilateral orchiectomy (i.e., surgical or medical castration). 4. Subject has disease progression by at least 1 of the following: a) PSA progression defined by a minimum of 2 rising PSA levels with an interval of at least 1 week between each draw; b) Bone disease progression as defined by Prostate Cancer Working Group 2 guidelines (at least 2 new lesions) on bone scan; or c) Soft tissue disease progression as defined by RECIST 1.1 5. For subjects who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the study. 6. Subject must have failed at least one course of androgen deprivation therapy (ADT), i.e., treatment with GnRH analogues. 7. Subject has an ECOG performance status of 0-2. 8. Subject has been evaluated by a local neurologist prior to study entry who has determined the subject has at least one risk factor for seizure including: a) past history of seizure due to any cause except a single febrile seizure in childhood. Patients with a history of seizures should not have had a seizure within 12 months of Screening and must have had no anticonvulsants for 12 months prior to Screening. b) history of cerebrovascular accident (CVA) or transient ischemic attack (TIA), c) history of traumatic brain or head injury with loss of consciousness, d) unexplained loss of consciousness within the last 12 months, e) presence of a space occupying lesion in the brain including previously treated brain metastasis(es) or primary CNS tumor, f) history of arteriovenous malformations of the brain, g) history of brain infection (i.e., abscess, meningitis, or encephalitis), h) current use of medication that may lower seizure threshold (see Appendix 12.1), i) presence of Alzheimer’s disease, meningioma, leptomeningeal disease from prostate cancer. 9. Male subject and his female partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period and for 3 months after final study drug administration. a) Two acceptable forms of birth control include: i. Condom (barrier method of contraception), AND ii. One of the following acceptable forms of contraception is required: 1. Established use of oral, injected or implanted hormonal methods of contraception. 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). 3. Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository). 4. Vasectomy or surgical castration at least 6 months prior to Screening. 10. Male subject must use a condom, if having sex with a pregnant woman. 11. Male subject must not donate sperm starting at Screening and throughout the study period and for at least 3 months after final drug administration. 12. Subject is able to swallow the study drug and comply with study requirements. 13. Subject agrees not to participate in another interventional study while on treatment. Waivers to the inclusion criteria will NOT be allowed. |
|
E.4 | Principal exclusion criteria |
Subject will be excluded from participation if any of the following apply: 1. Subject with a history of exposure to enzalutamide. 2. Subject has severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the subject inappropriate for enrollment. 3. Subject is currently treated with anti-epileptics. 4. Subject has a history of seizure in the past 12 months of Screening as assessed by neurology examination and history. 5. Subject with rapidly progressive visceral disease who has not received and is thought able to tolerate cytotoxic chemotherapy. (However, subject who has previously received cytotoxic chemotherapy is permitted). 6. Subject has clinical signs suggestive of high or imminent risks for pathological fracture, spinal cord compression and/or cauda equina syndrome. 7. Subject’s absolute neutrophil count is < 1500 /µL, platelet count is < 100,000/µL, or hemoglobin is < 5.6 mmol/L (9 g/dL) at Screening. 8. Subject’s total bilirubin is ≥ 1.5 x ULN (except for subjects with documented Gilbert’s disease) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is ≥ 2.5x ULN at Screening. 9. Subject’s estimated creatinine clearance (Cer) is less than 30 mL/min by the Cockcroft and Gault formula (Creatinine Clearance (mL/min) = (140 – age)(wt kg) / 72 x serum creatinine (mg/100 ml) [Cockcroft, 1976] at Screening. 10. Subject has uncontrolled hypertension as indicated by a resting systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg at Screening. 11. Subject has received an investigational agent within 4 weeks or 5 half lives whichever is longer prior to Day 1. 12. Subject has shown a hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene. 13. Subject has any condition which, in the Investigator’s opinion, makes the subject unsuitable for study participation. Waivers to the exclusion criteria will NOT be allowed.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of evaluable subjects with at least one confirmed seizure as adjudicated by the Independent Adjudication Committee (IAC) during the 4-month treatment duration. An evaluable subject is defined as a subject with a confirmed seizure during the 4-month treatment period of the study or who completed at least 3 months (75%) of the planned treatment. Only an enrolled subject who discontinues the study before completing 3 months on treatment may be replaced at the discretion of the Sponsor, however, an enrolled subject who is discontinued due to a confirmed seizure event will not be replaced. A cumulative summary to include all seizure events, including those occurring beyond the 4 month treatment period will be included. In case the drop-out rate is higher than expected, appropriate method such as Kaplan-Meier estimations may be considered. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The proportion of evaluable subjects with at least one confirmed seizure as adjudicated by the Independent Adjudication Committee (IAC) during the 4 month duration. |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 | No |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Chile |
Czech Republic |
Finland |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Israel |
Italy |
Korea, Republic of |
New Zealand |
Singapore |
Spain |
Sweden |
Taiwan |
United Kingdom |
United States |
|
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
|
The end of trial in all participating countries is defined as the Last Subject’s Last Visit. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |