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Metastatic Castration-resistant Prostate Cancer (mCRPC)Phase 4UPWARDNCT01977651

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

A Phase 4 study testing Enzalutamide in people with Metastatic Castration-resistant Prostate Cancer (mCRPC), run by Astellas Pharma Global Development, Inc. at 76 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Any age, men only
What is being tested?
Enzalutamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
424 participants
Where
76 sitesin 20 countries
Study dates
25 Sep 2013to 11 Jan 2019
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

76 sites in 20 countries.

76 sites in 20 countries

United States9 sites

  • Site US10005

    Anchorage, Alaska, 99503

  • Site US10008

    Dallas, Texas, 75231

  • Site US10024

    Detroit, Michigan, 48202

  • Site US10016

    Durham, North Carolina, 27710

  • Site US10001

    New York, New York, 10065

  • Site US10014

    New York, New York, 10065

  • Site US10025

    Seattle, Washington, 98109

  • Site US10039

    Syracuse, New York, 13210

  • Site US10026

    The Bronx, New York, 10461

Other trials in United States

Israel8 sites

  • Site IL97201

    Be’er Ya‘aqov, 70300

  • Site IL97203

    Beersheba, 84101

  • Site IL97205

    Haifa, 31096

  • Site IL97204

    Jerusalem, 91120

  • Site IL97202

    Kfar Saba, Central District, 44281

  • Site IL97208

    Nahariya, 21000

  • Site IL97206

    Petah Tikva, 49100

  • Site IL97207

    Ramat Gan, 52621

Other trials in Israel

Australia7 sites

  • Site AU61007

    Adelaide, South Australia, 5042

  • Site AU61004

    Ballarat, Victoria, 3350

  • Site AU61012

    Kogarah, New South Wales, 2217

  • Site AU61002

    Nambour, Queensland, 4560

  • Site AU61005

    Randwick, New South Wales, 2031

  • Site AU61011

    Sydney, New South Wales, 2109

  • Site AU61001

    Tweed Heads, New South Wales, 2485

Other trials in Australia

Argentina6 sites

  • Site AR54001

    Berazategui, Buenos Aires, B1880BBF

  • Site AR54002

    Buenos Aires, Buenos Aires F.D., C1120AAT

  • Site AR54006

    Ciudad Autonoma de BuenosAires, Buenos Aires, C1426ANZ

  • Site AR54003

    Córdoba, 5000

  • Site AR54005

    San Miguel de Tucumán, 4000

  • Site AR54004

    Santa Fe, S3000FFU

Other trials in Argentina

Spain6 sites

  • Site ES34003

    Barcelona, 08025

  • Site ES34004

    Barcelona, 08035

  • Site ES34007

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Site ES34006

    Madrid, 28050

  • Site ES34001

    Pamplona, Navarre, 31008

  • Site ES34005

    Sabadell, Barcelona, 08208

Other trials in Spain

Canada5 sites

  • Site CA15005

    Abbotsford British Columbia, British Columbia, V2S 3N5

  • Site CA15004

    Brampton, Ontario, L6T 4S5

  • Site CA15014

    Halifax, Nova Scotia, B3H 2Y9

  • Site CA15001

    Québec, Quebec, G1R3S1

  • Site CA15010

    Scarborough Village, Ontario, M1S 4V5

Other trials in Canada

South Korea5 sites

  • Site KR82006

    Seongnam-si, Gyeonggi-do, 013620

  • Site KR82007

    Seoul, 03080

  • Site KR82003

    Seoul, 135-710

  • Site KR82001

    Seoul, 135-720

  • Site KR82004

    Seoul, 137-701

Other trials in South Korea

Chile4 sites

  • Site CL56004

    Santiago, 8420383

  • Site CL56001

    Temuco, Araucania, 4810469

  • Site CL56002

    Temuco, 4781156

  • Site CL56003

    Viña del Mar, 2540364

Other trials in Chile

Italy4 sites

  • Site IT39002

    Arezzo, 52100

  • Site IT39001

    Cremona, Lombardy, 26100

  • Site IT39005

    Meldola, Emilia-Romagna, 47014

  • Site IT39003

    Roma, 00144

Other trials in Italy

Belgium3 sites

  • Site BE32004

    Anderlecht, 1070

  • Site BE32001

    Kortrijk, 8500

  • Site BE32003

    Liège, B-4000

Other trials in Belgium

Finland3 sites

  • Site FI35803

    Helsinki, 00290

  • Site FI35801

    Oulu, 90220

  • Site FI35802

    Tampere, 33520

Other trials in Finland

France3 sites

  • Site FR33002

    Lyon, 69437

  • Site FR33004

    Rouen, 76031

  • Site FR33005

    Suresnes, 92151

Other trials in France

Germany3 sites

  • Site DE49003

    Berlin, 12200

  • Site DE49001

    Münster, 48149

  • Site DE49009

    Nürtingen, Baden-Wurttemberg, 72622

Other trials in Germany

Czechia2 sites

  • Site CZ42004

    Prague, 12000

  • Site CZ42002

    Prague, 16000

Other trials in Czechia

Sweden2 sites

  • Site SE46001

    Gothenburg, 41345

  • Site SE46002

    Örebro, 701 85

Other trials in Sweden

Taiwan2 sites

  • Site TW88601

    Kaohsiung City, 81362

  • Site TW88603

    Taipei, 10048

Other trials in Taiwan

Hungary1 site

  • Site HU36002

    Sopron, Győr-Moson-Sopron, 9400

Other trials in Hungary

New Zealand1 site

  • Site NZ64001

    Hamilton, 3204

Other trials in New Zealand

Singapore1 site

  • Site SG65002

    Singapore, 119228

Other trials in Singapore

United Kingdom1 site

  • Site GB44002

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

About this study

Official 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

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.

Read the detailed description

This was a multicenter, single-arm, open-label, postmarketing safety study to evaluate the risk of seizure among patients with mCRPC treated with enzalutamide who were at potential increased risk of seizure.

Participants who met all inclusion and none of the exclusion criteria were enrolled into the study and participated in a 4-month treatment period, during which once daily dosing of enzalutamide (160 mg/day) occurred. At the end of the 4-month treatment period, participants who were assessed as deriving benefit from enzalutamide treatment were allowed to continue in the extension period where participants continued to receive enzalutamide until 1 of the following criteria was met:

  1. The participant experienced bone disease progression per Prostate Cancer Working Group 2 (PCWG2) guidelines or soft tissue disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  2. The participant initiated treatment with another anticancer therapy or, in the opinion of the investigator, continued dosing would have led to undue risk to the patient
  3. The participant met a discontinuation criterion
  4. The sponsor terminated the study

Participants who continued to receive clinical benefit from treatment with enzalutamide and did not meet any discontinuation criteria may have transitioned to an open label roll-over extension study upon approval of the study protocol at the institution where they were receiving treatment.

Participants who did not continue in the extension period or who met a discontinuation criterion were discontinued from enzalutamide therapy and completed a follow-up visit 30 days from the last dose of enzalutamide or prior to the initiation of another anticancer therapy, whichever occurred first.

For participants who continued on treatment after the 12-month extension period, data collection was limited to dosing information, concomitant medications, and all adverse events (AEs) including serious adverse events (SAEs).

Being tested
Enzalutamide
Keywords
enzalutamide, Xtandi, seizure, Central Nervous System, MDV3100, metastatic castration-resistant prostate cancer (mCRPC)
Medical subject headings
Seizures

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EnzalutamideDrug

    Also called Xtandi, MDV3100

    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.

Study groups in NCT01977651
Study groupRoleWhat they receive
Enzalutamide 160 mgExperimentalParticipants 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.
Receives: Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2013 (estimated)
  2. Study start25 Sep 2013
  3. Primary completion1 Feb 2016
  4. Study completion11 Jan 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
424 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01977651
Sponsor's protocol ID
9785-CL-0403
Other IDs
2013-003022-92, U1111-1157-0224
Acronym
UPWARD
Status last verified
Nov 2024
First submitted
31 Oct 2013
Last updated
6 Dec 2024
Data monitoring committee
Yes
Individual data sharing
No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Enzalutamide in people with Metastatic Castration-resistant Prostate Cancer (mCRPC), run by Astellas Pharma Global Development, Inc. at 76 sites in 20 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 sites in United States, Israel, Australia, Argentina, Spain and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Percentage of Evaluable Participants With at Least One Confirmed Seizure as Adjudicated by the Independent Adjudication Committee (IAC) (time frame: Day 1 up to week 17 (end of 4-month treatment period)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01977651.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2024.

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