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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01977651


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT01977651
Ethics application status
Date submitted
31/10/2013
Date registered
7/11/2013

Titles & IDs
Public title
A Study to Evaluate the Potential Increased Risk of Seizures Among Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated With Enzalutamide
Scientific title
A Multicenter, Single-arm, Open-label, Postmarketing 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
Secondary ID [1] 0 0
2013-003022-92
Secondary ID [2] 0 0
9785-CL-0403
Universal Trial Number (UTN)
Trial acronym
UPWARD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-resistant Prostate Cancer (mCRPC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Enzalutamide

Experimental: Enzalutamide 160 mg - 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.


Treatment: Drugs: Enzalutamide
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Percentage of Evaluable Participants With at Least One Confirmed Seizure as Adjudicated by the Independent Adjudication Committee (IAC)
Timepoint [1] 0 0
Day 1 up to week 17 (end of 4-month treatment period)

Eligibility
Key inclusion criteria
* 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:

1. 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;
2. Bone disease progression as defined by Prostate Cancer Working Group 2 guidelines (at least 2 new lesions) on bone scan; or
3. 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:

1. 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,
2. history of cerebrovascular accident (CVA) or transient ischemic attack (TIA),
3. history of traumatic brain or head injury with loss of consciousness
4. unexplained loss of consciousness within the last 12 months,
5. presence of a space occupying lesion in the brain including previously treated brain metastasis(es) or primary central nervous system (CNS) tumor,
6. history of arteriovenous malformations of the brain,
7. history of brain infection (i.e., abscess, meningitis, or encephalitis),
8. current use of medication that may lower seizure threshold
9. 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:
1. Condom (barrier method of contraception), AND
2. 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.
* 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.
Minimum age
No limit
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/01/2019
Sample size
Target
Accrual to date
Final
424
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Site AU61012 - Kogarah
Recruitment hospital [2] 0 0
Site AU61005 - Randwick
Recruitment hospital [3] 0 0
Site AU61011 - Sydney
Recruitment hospital [4] 0 0
Site AU61001 - Tweed Heads
Recruitment hospital [5] 0 0
Site AU61002 - Nambour
Recruitment hospital [6] 0 0
Site AU61007 - Adelaide
Recruitment hospital [7] 0 0
Site AU61004 - Ballarat
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2109 - Sydney
Recruitment postcode(s) [4] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [5] 0 0
4560 - Nambour
Recruitment postcode(s) [6] 0 0
5042 - Adelaide
Recruitment postcode(s) [7] 0 0
3350 - Ballarat
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Argentina
State/province [7] 0 0
Buenos Aires
Country [8] 0 0
Argentina
State/province [8] 0 0
Caba
Country [9] 0 0
Argentina
State/province [9] 0 0
Cordoba
Country [10] 0 0
Argentina
State/province [10] 0 0
Santa Fe
Country [11] 0 0
Argentina
State/province [11] 0 0
Tucuman
Country [12] 0 0
Belgium
State/province [12] 0 0
Anderlecht
Country [13] 0 0
Belgium
State/province [13] 0 0
Kortrijk
Country [14] 0 0
Belgium
State/province [14] 0 0
Liege
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Nova Scotia
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
Chile
State/province [19] 0 0
IX Region
Country [20] 0 0
Chile
State/province [20] 0 0
Santiago
Country [21] 0 0
Chile
State/province [21] 0 0
Temuco
Country [22] 0 0
Chile
State/province [22] 0 0
Vina del Mar
Country [23] 0 0
Czechia
State/province [23] 0 0
Praha 2
Country [24] 0 0
Czechia
State/province [24] 0 0
Praha 6
Country [25] 0 0
Finland
State/province [25] 0 0
Helsinki
Country [26] 0 0
Finland
State/province [26] 0 0
Oulu
Country [27] 0 0
Finland
State/province [27] 0 0
Tampere
Country [28] 0 0
France
State/province [28] 0 0
Lyon Cedex 03
Country [29] 0 0
France
State/province [29] 0 0
Rouen Cedex
Country [30] 0 0
France
State/province [30] 0 0
Suresnes
Country [31] 0 0
Germany
State/province [31] 0 0
Baden-Württemberg
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Germany
State/province [33] 0 0
Munster
Country [34] 0 0
Hungary
State/province [34] 0 0
Gyor-Moson Sopron
Country [35] 0 0
Israel
State/province [35] 0 0
HaMerkaz
Country [36] 0 0
Israel
State/province [36] 0 0
Be'er Ya'akov
Country [37] 0 0
Israel
State/province [37] 0 0
Beer-Sheva
Country [38] 0 0
Israel
State/province [38] 0 0
Haifa
Country [39] 0 0
Israel
State/province [39] 0 0
Jerusalem
Country [40] 0 0
Israel
State/province [40] 0 0
Nahariya
Country [41] 0 0
Israel
State/province [41] 0 0
Petah-Tiqva
Country [42] 0 0
Israel
State/province [42] 0 0
Ramat Gan
Country [43] 0 0
Italy
State/province [43] 0 0
Emilia-Romagna
Country [44] 0 0
Italy
State/province [44] 0 0
Lombardia
Country [45] 0 0
Italy
State/province [45] 0 0
Arezzo
Country [46] 0 0
Italy
State/province [46] 0 0
Roma
Country [47] 0 0
Korea, Republic of
State/province [47] 0 0
Gyeonggi-do
Country [48] 0 0
Korea, Republic of
State/province [48] 0 0
Seoul
Country [49] 0 0
New Zealand
State/province [49] 0 0
Hamilton
Country [50] 0 0
Singapore
State/province [50] 0 0
Singapore
Country [51] 0 0
Spain
State/province [51] 0 0
Barcelona
Country [52] 0 0
Spain
State/province [52] 0 0
Navarra
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
Country [54] 0 0
Sweden
State/province [54] 0 0
Goteborg
Country [55] 0 0
Sweden
State/province [55] 0 0
Orebro
Country [56] 0 0
Taiwan
State/province [56] 0 0
Kaohsiung
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taipei City
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Astellas Pharma Global Development, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sr. Medical Director
Address 0 0
Astellas Pharma Global Development, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01977651

Additional trial details provided through ANZCTR
Accrual to date
Recruitment state(s)
Funding & Sponsors
Primary sponsor
Primary sponsor name
Primary sponsor address
Primary sponsor country
Ethics approval
Ethics application status
 
Public notes
See EudraCT for results (EudraCT number 2013-003022-92)

Contacts
Principal investigator
Title 117 0
Name 117 0
Address 117 0
Country 117 0
Phone 117 0
Fax 117 0
Email 117 0
Contact person for public queries
Title 118 0
Name 118 0
Address 118 0
Country 118 0
Phone 118 0
Fax 118 0
Email 118 0
Contact person for scientific queries
Title 119 0
Name 119 0
Address 119 0
Country 119 0
Phone 119 0
Fax 119 0
Email 119 0