A Study to Evaluate the Potential Increased Risk of Seizures Among Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated With Enzalutamide

NCT01977651 | Completed Phase 4 Results DMC

• 3 other identifiers: 9785-CL-04032013-003022-92U1111-1157-0224
• Study Type: interventional
• Target: 424
• Locations: 20 countries
• Sites: 76

Brief Summary

The objective of this study was to evaluate the incidence of seizures and monitor the safety of enzalutamide treatment in participants with metastatic castration-resistant prostate cancer (mCRPC) known to have risk factor(s) for seizure.

Conditions

Metastatic Castration-resistant Prostate Cancer (mCRPC)

Keywords

enzalutamide; Xtandi; seizure; Central Nervous System; MDV3100; metastatic castration-resistant prostate cancer (mCRPC)

Outcome Measures

Primary Outcomes (1)

• The Percentage of Evaluable Participants With at Least One Confirmed Seizure as Adjudicated by the Independent Adjudication Committee (IAC)

  Percentage of evaluable participants with at least one confirmed seizure as adjudicated by the IAC during the first 4 months of treatment were reported.

  Day 1 up to week 17 (end of 4-month treatment period)

Study Arms (1)

Enzalutamide 160 mg

EXPERIMENTAL

Participants received 160 mg of enzalutamide orally once a day, for 4 months. At the end of the 4-month treatment period, participants who were assessed as deriving benefit from enzalutamide treatment continued in the extension period. The total study drug treatment duration for the extended period depended on individual clinical benefit. If a participant experienced a Grade 3 or higher toxicity that was attributed to enzalutamide and could not be ameliorated by the use of adequate medical intervention, treatment with enzalutamide was allowed to be interrupted for 1 week or until the toxicity grade improved to Grade 2 or lower severity. Subsequently, enzalutamide was restarted at the original dose 160 mg per day or a reduced dose 120 or 80 mg per day in consultation with the medical monitor.

Drug: Enzalutamide

Interventions

Enzalutamide DRUG

Participants received 4 capsules (40 mg each) of enzalutamide orally once a day, for a total daily dose of 160 mg. Treatment was given with or without food and as close as possible to the same time each day.

Also known as: Xtandi, MDV3100

Enzalutamide 160 mg

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Medivation LLC, a wholly owned subsidiary of Pfizer Inc.: collaborator

Study Sites (76)

Site US10005

Anchorage, Alaska, 99503, United States

Location

Site US10024

Detroit, Michigan, 48202, United States

Location

Site US10001

New York, New York, 10065, United States

Location

Site US10014

New York, New York, 10065, United States

Location

Site US10039

Syracuse, New York, 13210, United States

Location

Site US10026

The Bronx, New York, 10461, United States

Location

Site US10016

Durham, North Carolina, 27710, United States

Location

Site US10008

Dallas, Texas, 75231, United States

Location

Site US10025

Seattle, Washington, 98109, United States

Location

Site AR54001

Berazategui, Buenos Aires, B1880BBF, Argentina

Location

Site AR54006

Ciudad Autonoma de BuenosAires, Buenos Aires, C1426ANZ, Argentina

Location

Site AR54002

Buenos Aires, Buenos Aires F.D., C1120AAT, Argentina

Location

Site AR54003

Córdoba, 5000, Argentina

Location

Site AR54005

San Miguel de Tucumán, 4000, Argentina

Location

Site AR54004

Santa Fe, S3000FFU, Argentina

Location

Site AU61012

Kogarah, New South Wales, 2217, Australia

Location

Site AU61005

Randwick, New South Wales, 2031, Australia

Location

Site AU61011

Sydney, New South Wales, 2109, Australia

Location

Site AU61001

Tweed Heads, New South Wales, 2485, Australia

Location

Site AU61002

Nambour, Queensland, 4560, Australia

Location

Site AU61007

Adelaide, South Australia, 5042, Australia

Location

Site AU61004

Ballarat, Victoria, 3350, Australia

Location

Site BE32004

Anderlecht, 1070, Belgium

Location

Site BE32001

Kortrijk, 8500, Belgium

Location

Site BE32003

Liège, B-4000, Belgium

Location

Site CA15005

Abbotsford, British Columbia, V2S 3N5, Canada

Location

Site CA15014

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Site CA15004

Brampton, Ontario, L6T 4S5, Canada

Location

Site CA15010

Scarborough Village, Ontario, M1S 4V5, Canada

Location

Site CA15001

Québec, Quebec, G1R3S1, Canada

Location

Site CL56001

Temuco, Región de la Araucanía, 4810469, Chile

Location

Site CL56004

Santiago, 8420383, Chile

Location

Site CL56002

Temuco, 4781156, Chile

Location

Site CL56003

Viña del Mar, 2540364, Chile

Location

Site CZ42004

Prague, 12000, Czechia

Location

Site CZ42002

Prague, 16000, Czechia

Location

Site FI35803

Helsinki, 00290, Finland

Location

Site FI35801

Oulu, 90220, Finland

Location

Site FI35802

Tampere, 33520, Finland

Location

Site FR33002

Lyon, 69437, France

Location

Site FR33004

Rouen, 76031, France

Location

Site FR33005

Suresnes, 92151, France

Location

Site DE49009

Nürtingen, Baden-Wurttemberg, 72622, Germany

Location

Site DE49003

Berlin, 12200, Germany

Location

Site DE49001

Münster, 48149, Germany

Location

Site HU36002

Sopron, Győr-Moson-Sopron, 9400, Hungary

Location

Site IL97202

Kfar Saba, Central District, 44281, Israel

Location

Site IL97203

Beersheba, 84101, Israel

Location

Site IL97201

Be’er Ya‘aqov, 70300, Israel

Location

Site IL97205

Haifa, 31096, Israel

Location

Site IL97204

Jerusalem, 91120, Israel

Location

Site IL97208

Nahariya, 21000, Israel

Location

Site IL97206

Petah Tikva, 49100, Israel

Location

Site IL97207

Ramat Gan, 52621, Israel

Location

Site IT39005

Meldola, Emilia-Romagna, 47014, Italy

Location

Site IT39001

Cremona, Lombardy, 26100, Italy

Location

Site IT39002

Arezzo, 52100, Italy

Location

Site IT39003

Roma, 00144, Italy

Location

Site NZ64001

Hamilton, 3204, New Zealand

Location

Site SG65002

Singapore, 119228, Singapore

Location

Site KR82006

Seongnam-si, Gyeonggi-do, 013620, South Korea

Location

Site KR82007

Seoul, 03080, South Korea

Location

Site KR82003

Seoul, 135-710, South Korea

Location

Site KR82001

Seoul, 135-720, South Korea

Location

Site KR82004

Seoul, 137-701, South Korea

Location

Site ES34007

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Site ES34005

Sabadell, Barcelona, 08208, Spain

Location

Site ES34001

Pamplona, Navarre, 31008, Spain

Location

Site ES34003

Barcelona, 08025, Spain

Location

Site ES34004

Barcelona, 08035, Spain

Location

Site ES34006

Madrid, 28050, Spain

Location

Site SE46001

Gothenburg, 41345, Sweden

Location

Site SE46002

Örebro, 701 85, Sweden

Location

Site TW88601

Kaohsiung City, 81362, Taiwan

Location

Site TW88603

Taipei, 10048, Taiwan

Location

Site GB44002

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Links

• Link to results on the Astellas Clinical Study Results website.

MeSH Terms

Conditions

Seizures

Interventions

enzalutamide

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

After completing the extension period participants who were assessed to benefit from enzalutamide completed their treatment in another Astellas study, 9785-CL-0123 (NCT02960022).

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc.

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Sr. Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 7, 2013
• Study Start: September 25, 2013
• Primary Completion: February 1, 2016
• Study Completion: January 11, 2019
• Last Updated: December 6, 2024
• Results First Posted: December 9, 2020

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); IL (8); ES (6); BE (3); SG (1); HU (1); AU (7); AR (6); NZ (1); CL (4); CA (5); SE (2); GB (1); FI (3); US (9); FR (3); IT (4); CZ (2); KR (5); TW (2)