A study to evaluate the risk of seizures among metastatic Castration-Resistant Prostate Cancer (mCRPC) patients treated with enzalutamide
- Conditions
- Medical condition: metastatic castration-resistant prostate cancer (mCRPC)MedDRA version: 19.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003022-92-SE
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 400
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).
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method