A Study to Evaluate the Potential Increased Risk of Seizures Among Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated With Enzalutamide
Verified June 2014 by Astellas Pharma Inc
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
First received: October 31, 2013
Last updated: June 20, 2014
Last verified: June 2014
The objective of this study is to evaluate the incidence of seizures and monitor the safety of enzalutamide treatment in subjects with metastatic castration-resistant prostate cancer known to have risk factor(s) for seizure.
Metastatic Castration- Resistant Prostate Cancer (mCRCP)
||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Multicenter, Single-Arm, Open-Label, Post-Marketing Safety Study to Evaluate the Risk of Seizure Among Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated With Enzalutamide Who Are at Potential Increased Risk of Seizure
Primary Outcome Measures:
- The proportion of evaluable subjects with at least one confirmed seizure as adjudicated by the Independent Adjudication Committee (IAC) [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||June 2018 (Final data collection date for primary outcome measure)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Subject has histologically confirmed metastatic adenocarcinoma of the prostate.
- Subject has ongoing androgen deprivation therapy with a Gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) or bilateral orchiectomy (i.e., surgical or medical castration).
Subject has disease progression by at least one of the following:
- Prostate-Specific Antigen (PSA) progression defined by a minimum of 2 rising PSA levels with an interval of at least 1 week between each draw;
- Bone disease progression as defined by Prostate Cancer Working Group 2 guidelines (at least 2 new lesions) on bone scan; or
- Soft tissue disease progression as defined by RECIST 1.1
- 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.
- Subject must have failed at least one course of androgen deprivation therapy (ADT), i.e., treatment with GnRH analogues.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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:
- 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,
- history of cerebrovascular accident (CVA) or transient ischemic attack (TIA),
- history of traumatic brain or head injury with loss of consciousness
- unexplained loss of consciousness within the last 12 months,
- presence of a space occupying lesion in the brain including previously treated brain metastasis(es) or primary central nervous system (CNS) tumor,
- history of arteriovenous malformations of the brain,
- history of brain infection (i.e., abscess, meningitis, or encephalitis),
- current use of medication that may lower seizure threshold
- presence of Alzheimer's disease, meningioma, leptomeningeal disease from prostate cancer.
- Subject is able to swallow the study drug and comply with study requirements.
- Subject agrees not to participate in another interventional study while on treatment.
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.
1. Two acceptable forms of birth control include:
- Condom (barrier method of contraception), AND
One of the following acceptable forms of contraception is required:
- Established use of oral, injected or implanted hormonal methods of contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository).
- Vasectomy or surgical castration at least 6 months prior to Screening.
- Male subject must use a condom, if having sex with a pregnant woman.
- Male subject must not donate sperm starting at Screening and throughout the study period and for at least 3 months after final drug administration.
- Subject with a history of exposure to enzalutamide.
- Subject has severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the subject inappropriate for enrollment.
- Subject is currently being treated with anti-epileptics.
- Subject has a history of seizure within the past 12 months of Screening as assessed by neurology examination and history.
- Subject with rapidly progressing visceral disease who has not received and is thought to be able to tolerate cytotoxic chemotherapy. (However, subject who has previously received cytotoxic chemotherapy is permitted).
- Subject has clinical signs suggestive of high or imminent risks for pathological fracture, spinal cord compression and/or cauda equina syndrome.
- Subject's absolute neutrophil count is < 1500/microliter (µL), platelet count is < 100,000/µL) or hemoglobin is < 5.6 millimoles(mmol)/liter (L) (9 grams (g)/deciliter (dL) at Screening.
- Subject's total bilirubin is ≥ 1.5 x upper limit of normal (ULN) (except for subjects with documented Gilbert's disease) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is ≥ 2.5x upper limit of normal (ULN) at Screening.
- Subject's estimated creatinine clearance (Cer) is less than 30 milliliter (mL)/minute (min) by the Cockcroft and Gault formula (Creatinine Clearance (mL/min) = (140 - age)(weight (wt) kilogram (kg) / 72 x serum creatinine (milligram (mg)/100 mL) [Cockcroft, 1976] at Screening.
- Subject has uncontrolled hypertension as indicated by a resting systolic blood pressure > 160 millimeter of mercury (mmHg) or diastolic blood pressure > 100 millimeter of mercury (mmHg) at Screening.
- Subject has received an investigational agent within 4 weeks or 5 half lives whichever is longer prior to Day 1.
- Subject has shown a hypersensitivity reaction to the active pharmaceutical ingredient or any of the capsule components, including Labrasol, butylated hydroxyanisole, and butylated hydroxytoluene.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01977651
Astellas Pharma Global Development, Inc.
||Sr. Medical Director
||Astellas Pharma Global Development, Inc.
No publications provided
||Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
History of Changes
|Other Study ID Numbers:
||9785-CL-0403, 2013-003022-92, U1111-1157-0224
|Study First Received:
||October 31, 2013
||June 20, 2014
||United States: Food and Drug Administration
Canada: Health Canada
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Sweden: Medical Products Agency
Italy: The Italian Medicines Agency
Czech Republic: State Institute for Drug Control
Australia: Department of Health and Ageing Therapeutic Goods Administration
South Korea: Korea Food and Drug Administration (KFDA)
Hong Kong: Department of Health
Singapore: Ministry of Health
New Zealand: Medsafe
Israel: Ministry of Health
Taiwan : Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Chile: Ministry of Health
Finland: Finnish Medicines Agency
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
Keywords provided by Astellas Pharma Inc:
metastatic castration-resistant prostate cancer (mCRCP)
Central Nervous System
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 20, 2014
Genital Neoplasms, Male
Neoplasms by Site
Genital Diseases, Male
Central Nervous System Diseases
Nervous System Diseases
Signs and Symptoms