A Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
- Conditions
- Metastatic Hormone Sensitive Prostate Cancer
- Interventions
- Drug: Placebo
- Registration Number
- NCT02677896
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
The purpose of this study was to evaluate the efficacy of enzalutamide plus androgen deprivation therapy (ADT) as measured by radiographic progression-free survival (rPFS) based on central review. The study also evaluated the safety of enzalutamide plus ADT in mHSPC.
- Detailed Description
Following unblinding at the end of the double-blind period and demonstration of a statistically significant advantage of enzalutamide over placebo when added to ADT as assessed by the primary endpoint of rPFS, subjects were eligible to transition to an open-label portion of the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 1150
- Subject is considered an adult according to local regulation at the time of signing informed consent.
- Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell or small cell histology.
- Subject has metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan (for soft tissue). Subjects whose disease spread is limited to regional pelvic lymph nodes are not eligible.
- Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical castration).
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Inclusion Criteria for Open-Label Extension:
- Subject received randomized double-blind treatment in ARCHES
- Subject has not met any of the discontinuation criteria in the main ARCHES protocol
- Subject is willing to maintain ADT with LHRH agonist or antagonist or has had a bilateral orchiectomy.
- Subject is able to swallow enzalutamide capsules whole and to comply with study requirements throughout the study
- Subject and subject's female partner agree to follow contraception and sperm donation requirements in main protocol
-
Subject has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer (the following exceptions are permitted):
- Up to 3 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
- Subject may have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to day 1;
- Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of day 1 and no evidence of disease progression during or after the completion of docetaxel therapy;
- Up to 6 months of ADT with LHRH agonists or antagonists or orchiectomy with or without concurrent antiandrogens prior to day 1 if subject was treated with docetaxel, with no radiographic evidence of disease progression or rising PSA levels prior to day 1;
- Prior ADT given for < 39 months in duration and > 9 months before randomization as neoadjuvant/adjuvant therapy.
-
Subject had a major surgery within 4 weeks prior to day 1.
-
Subject received treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks prior to day 1.
-
Subject received treatment with estrogens, cyprotoerone acetate or androgens within 4 weeks prior to day 1.
-
Subject received treatment with systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to day 1, intended for the treatment of prostate cancer.
-
Subject received treatment with herbal medications that have known hormonal antiprostate cancer activity and/or are known to decrease PSA levels within 4 weeks prior to day 1.
-
Subject received prior aminoglutethimide, ketoconazole, abiraterone acetate or enzalutamide for the treatment of prostate cancer or participation in a clinical study of an investigational agent that inhibits the AR or androgen synthesis (e.g., TAK-700, ARN-509, ODM-201).
-
Subject has known or suspected brain metastasis or active leptomeningeal disease.
-
Subject has absolute neutrophil count < 1500/μL, platelet count < 100000/μL or hemoglobin < 10 g/dL (6.2 mmol/L).
-
Subject has total bilirubin (TBL) ≥ 1.5 x the upper limit of normal (ULN) (except subjects with documented Gilbert's disease), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 x the ULN .
-
Subject has creatinine > 2 mg/dL (177 μmol/L).
-
Subject has albumin < 3.0 g/dL (30 g/L).
-
Subject has a history of seizure or any condition that may predispose to seizure.
-
Subject has history of loss of consciousness or transient ischemic attack within 12 months prior to day 1.
-
Subject has clinically significant cardiovascular disease.
-
Subject received bisphosphonates or denosumab within 2 weeks prior to day 1 unless administered at stable dose or to treat diagnosed osteoporosis
Exclusion Criteria for Open-Label Extension:
- Subject has taken commercially available enzalutamide (Xtandi).
- Subject's disease has progressed radiographically during the double-blind period of the study and treatment with study drug was stopped prior to study-wide unblinding. (Note: Subjects who progressed radiographically while in the double-blind portion of the study and continued treatment per protocol are allowed to participate in the open label extension.)
- After study-wide unblinding, subject has started any new investigational agent or anti-neoplastic therapy intended to treat prostate cancer
- Subject has any clinically significant disorder or condition including excessive alcohol or drug abuse, or secondary malignancy, which may interfere with study participation
- Subject has current or previously treated brain metastasis or active leptomeningeal disease
- Subject has a history of seizure or any condition that may increase the risk of seizure
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Androgen Deprivation Therapy (ADT) Placebo Participants received matching placebo orally once daily during double-blind treatment period until radiographic progression was documented or until the participants started an investigational agent or new therapy for treatment of prostate cancer or until any other discontinuation criterion was met. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock. Enzalutamide + Androgen Deprivation Therapy (ADT) Enzalutamide Participants received 160 mg enzalutamide orally once daily during double-blind treatment period until radiographic progression was documented or until the participants started an investigational agent or new therapy for treatment of prostate cancer or until any other discontinuation criterion was met. Eligible participants who received enzalutamide during double-blind treatment period and provided informed consent to take part in open-label period continued to receive 160 mg enzalutamide orally once daily in open-label period until disease progression, unacceptable toxicity or any other discontinuation criteria were met. ADT (either bilateral orchiectomy or Luteinizing hormone-releasing hormone (LHRH) agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock. Placebo followed by Enzalutamide Enzalutamide Eligible participants who received enzalutamide matching placebo during double-blind treatment period and provided informed consent to take part in open-label period switched to receive 160 mg enzalutamide orally once daily in open-label period until disease progression, unacceptable toxicity or any other discontinuation criteria were met. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
- Primary Outcome Measures
Name Time Method Radiographic Progression-Free Survival (rPFS) Based on Independent Central Review (ICR) of Bone Scan According to Prostate Cancer Clinical Trials Working Group 2 (PCWG2) Criteria From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months rPFS was calculated as the time from the date of randomization to the first objective evidence of radiographic progression disease (rPD) at any time or death up to 24 weeks after study drug discontinuation without documented radiographic progression, whichever occurred first. rPD was defined as progressive disease by Response Evaluation Criteria in Solid Tumors version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan compared to baseline or week 13 according to PCWG2 criteria, as assessed by ICR or death. In participants with no rPFS event, rPFS was censored on the date of last evaluable radiographic assessment prior to the data analysis cutoff date. In participants with no baseline radiographic assessment, participants with no postbaseline radiographic assessments and participants with all postbaseline radiographic assessments documented as "not evaluable (NE)," rPFS was censored on the date of randomization.
rPFS Based on ICR of Bone Scan According to Protocol Assessment Criteria From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months. rPFS was calculated as the time from the date of randomization to the first objective evidence of radiographic progression disease (rPD) at any time or death up to 24 weeks after study drug discontinuation without documented radiographic progression, whichever occurred first. rPD was defined as progressive disease by Response Evaluation Criteria in Solid Tumors version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan compared to baseline for week 13 or the best response on treatment for week 25 or later assessments, as assessed by ICR or death. In participants with no rPFS event, rPFS was censored on the date of last evaluable radiographic assessment prior to the data analysis cutoff date. In participants with no baseline radiographic assessment, participants with no postbaseline radiographic assessments and participants with all postbaseline radiographic assessments documented as "not evaluable (NE)," rPFS was censored on the date of randomization.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From date of randomization to OS final analysis (28 May 2021); Maximum treatment duration was 58.6 months OS was defined as the time from randomization to death due to any cause. In participants still alive at the date of the analysis cutoff point, OS was censored on the last date the participant was known to be alive. OS was analyzed using Kaplan-Meier estimates.
Time to Prostate Specific Antigen (PSA) Progression From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months Time to PSA progression was calculated as the time from the date of randomization to the first observation of PSA progression. A PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir, which was confirmed by a second consecutive value at least 3 weeks later. In participants with no PSA progression, time to PSA progression was censored on the date of the last PSA sample taken (or last value prior to 2 or more consecutive missed PSA assessments).
Time to Start of New Antineoplastic Therapy From date of randomization to data cut-off date (28 May 2021); Maximum treatment duration was 58.6 months In participants with a new antineoplastic therapy initiated for prostate cancer after randomization, time to start of a new antineoplastic therapy was defined as the time interval from randomization to the date of the first dose administration of the first antineoplastic therapy. In participants with no new antineoplastic therapy initiated for prostate cancer after randomization, time to start of new antineoplastic therapy was censored on the last visit date or the date of randomization, whichever occurred last. Time to start of new antineoplastic therapy was analyzed using Kaplan-Meier estimates.
PSA Undetectable Rate Up to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months The PSA undetectable rate was defined as the percentage of participants with undetectable (\< 0.2 ng/mL) PSA values at any time during study treatment, of those participants with detectable (≥ 0.2 ng/mL) PSA values at baseline.
Objective Response Rate (ORR) Up to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months The ORR was calculated as the percentage of participants who achieved a completed response (CR) or a partial response (PR) (unconfirmed responses) in their soft tissue disease using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by ICR.
Time to Deterioration in Urinary Symptoms From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months In participants with deterioration, the time to deterioration was calculated as the time interval between randomization and the first deterioration in urinary symptoms at any postbaseline visit. A deterioration in urinary symptoms was defined as an increase in the Quality of Life Prostate-specific Questionnaire (QLQ-PR25) modified urinary symptoms. Subscale score by ≥ 50% of the standard deviation observed in the QLQ-PR25 modified urinary symptoms subscale score at baseline. Modified urinary symptoms subscale score consisted of 3-items (Q31 - Q33) from the QLQ-PR25, each scored from 1 (not at all) to 4 (very much). The total modified urinary symptoms subscale score ranges from 0-100, with higher scores represents a higher level of symptomatology/problems. In participants without deterioration in urinary symptoms, the time to deterioration in urinary symptoms was censored on the date the last urinary symptoms QLQ-PR25 score was calculable.
Time to First Symptomatic Skeletal Event (SSE) From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months Time to first SSE was calculated as the time from randomization to the occurrence of the first SSE prior to the data analysis cut-off date. An SSE was defined as radiation to bone, surgery to bone, clinically apparent pathological bone fracture, or spinal cord compression. In participants with no SSE by the time of the data cut-off point, time to SSE was censored on the last visit date or the date of randomization, whichever occurred last.
Time to Castration Resistance From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months Time to castration resistance was calculated as the time from randomization to the first castration-resistant event. A castration resistance event was defined as any of the following in the presence of castrate levels of testosterone (\< 50 ng/dL): radiographic disease progression, PSA progression or SSE, whichever occurred first. In participants with no documented castration resistance event, the time to castration resistance was censored on the latest date from: the date of last radiologic assessment, the last PSA sample taken prior to the start of any new prostate cancer therapy and prior to 2 or more consecutive missed PSA assessments (if applicable), and the last visit date performed.
Time to Deterioration of Quality of Life (QoL) in Functional Assessment of Cancer Therapy-Prostate (FACT-P) From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months Time to deterioration of QoL was calculated as the time interval from the date of randomization to the first date a decline from baseline of 10 points or more in the FACT-P total score was recorded. The FACT-P consists of 27 core items that assess participant function in 4 domains and 12 prostate cancer-related items grouped into 5 subscales as follows: physical wellbeing, social/family wellbeing, emotional wellbeing, functional wellbeing and prostate cancer subscale. Each item is rated on a 0 to 4 Likert-type scale. The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0 to 156), where high score represent better quality of life. In participants without FACT-P progression, the time to deterioration of QoL was censored on the date of the last FACT-P total score was calculable.
Time to Pain Progression Based on Brief Pain Inventory-Short Form (BPI-SF) From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months Time to pain progression was defined as time from randomization to the first pain progression event. Pain progression was defined as an increase of ≥ 30% from baseline in the average BPI-SF pain severity score. BPI-SF contains 9 questions with rating scales from 0 (no pain/no interference) to 10 (worst pain/interferes completely). Total score was calculated as the average of each question. Higher scores represent a higher level of pain or interference. In participants with no pain progression event, time to pain progression was censored on the last visit date where BPI-SF was collected.
Trial Locations
- Locations (203)
Site CL56003
🇨🇱Santiago, Chile
Site US10060
🇺🇸Greenville, North Carolina, United States
Site CA15010
🇨🇦Brampton, Ontario, Canada
Site CA15021
🇨🇦Kingston, Ontario, Canada
Site CA15020
🇨🇦Toronto, Ontario, Canada
Site BE32012
🇧🇪Gent, Oost-Vlaanderen, Belgium
Site NL31010
🇳🇱Alkmaar, Noord-Holland, Netherlands
Site GB44002
🇬🇧Withington, Manchester, United Kingdom
Site DK45002
🇩🇰Copenhagen, Hovestaden, Denmark
Site DK45005
🇩🇰Aarhus, Midtjylland, Denmark
Site DK45004
🇩🇰Aalborg, Nordjylland, Denmark
Site US10050
🇺🇸Denver, Colorado, United States
Site US10059
🇺🇸Nashville, Tennessee, United States
Site JP81013
🇯🇵Kita-gun, Kagawa, Japan
Site JP81001
🇯🇵Maebashi, Gunma, Japan
Site JP81015
🇯🇵Fukuoka, Japan
Site JP81002
🇯🇵Chiba, Japan
Site JP81017
🇯🇵Ube, Yamaguchi, Japan
Site JP81018
🇯🇵Nagasaki, Japan
Site JP81020
🇯🇵Niigata, Japan
Site SK42107
🇸🇰Trencin, Slovakia
Site US10007
🇺🇸Anchorage, Alaska, United States
Site US10016
🇺🇸Homewood, Alabama, United States
Site US10008
🇺🇸Tucson, Arizona, United States
Site US10015
🇺🇸Chicago, Illinois, United States
Site US10043
🇺🇸Springfield, Illinois, United States
Site US10014
🇺🇸Durham, North Carolina, United States
Site US10011
🇺🇸Lancaster, Pennsylvania, United States
Site AU61016
🇦🇺Camperdown, New South Wales, Australia
Site CA15016
🇨🇦Edmonton, Alberta, Canada
Site AU61004
🇦🇺Ballarat, Victoria, Australia
Site AU61006
🇦🇺Sydney, New South Wales, Australia
Site AU61009
🇦🇺Tweed Heads, New South Wales, Australia
Site JP81014
🇯🇵Fukuoka, Japan
Site FI35802
🇫🇮Helsinki, Etelä-Suomen Lääni, Finland
Site FR33010
🇫🇷Angers, Maine-et-Loire, France
Site FI35805
🇫🇮Oulu, Finland
Site JP81005
🇯🇵Shinjuku-ku, Tokyo, Japan
Site JP81004
🇯🇵Koto-ku, Tokyo, Japan
Site JP81010
🇯🇵Abeno-ku, Osaka, Japan
Site IL97210
🇮🇱Beer-Sheva, Israel
Site JP81016
🇯🇵Sendai, Miyagi, Japan
Site JP81011
🇯🇵Chuo-ku, Osaka, Japan
Site DE49013
🇩🇪Heidelberg, Germany
Site JP81003
🇯🇵Sakura, Chiba, Japan
Site KR82002
🇰🇷Seoul, Korea, Republic of
Site IT39004
🇮🇹Cremona, Lombardia, Italy
Site IT39009
🇮🇹Candiolo, Italy
Site JP81006
🇯🇵Bunkyo-ku, Tokyo, Japan
Site JP81019
🇯🇵Yamagata, Japan
Site JP81012
🇯🇵Osakasayama, Osaka, Japan
Site NL31003
🇳🇱Nijmegen, Gelderland, Netherlands
Site KR82007
🇰🇷Busan, Korea, Republic of
Site NZ64004
🇳🇿Hamilton, New Zealand
Site NZ64003
🇳🇿Tauranga, Bay Of Plenty, New Zealand
Site RO40007
🇷🇴Brasov, Romania
Site SK42109
🇸🇰Kosice, Slovakia
Site RU70012
🇷🇺St. Petersburg, Russian Federation
Site RU70009
🇷🇺St. Petersburg, Russian Federation
Site RU70008
🇷🇺St. Petersburg, Russian Federation
Site ES34006
🇪🇸Pamplona, Navarra, Spain
Site SK42110
🇸🇰Bratislava, Slovakia
Site ES34011
🇪🇸Salamanca, A Coruña, Spain
Site RU70016
🇷🇺St. Petersburg, Russian Federation
Site ES34014
🇪🇸Barcelona, Cataluña, Spain
Site ES34001
🇪🇸Avila, Spain
Site SK42103
🇸🇰Nitra, Slovakia
Site SK42101
🇸🇰Poprad, Slovakia
Site TW88606
🇨🇳Taichung, Taiwan
Site ES34007
🇪🇸Barcelona, Spain
Site SE46004
🇸🇪Sundsvall, Vasternorrlands Lan, Sweden
Site ES34013
🇪🇸Valencia, Comunidad Valenciana, Spain
Site KR82003
🇰🇷Seoul, Korea, Republic of
Site US10036
🇺🇸Omaha, Nebraska, United States
Site AR54010
🇦🇷Buenos Aires, Argentina
Site US10035
🇺🇸Aurora, Colorado, United States
Site US10034
🇺🇸Fountain Valley, California, United States
Site US10056
🇺🇸La Jolla, California, United States
Site US10048
🇺🇸Saint Petersburg, Florida, United States
Site US10054
🇺🇸Thomasville, Georgia, United States
Site US10017
🇺🇸Towson, Maryland, United States
Site US10045
🇺🇸Jeffersonville, Indiana, United States
Site US10020
🇺🇸West Des Moines, Iowa, United States
Site US10018
🇺🇸Lawrenceville, New Jersey, United States
Site US10055
🇺🇸Kansas City, Kansas, United States
Site US10025
🇺🇸Newburgh, New York, United States
Site US10068
🇺🇸Charlotte, North Carolina, United States
Site US10009
🇺🇸Concord, North Carolina, United States
Site US10029
🇺🇸Syracuse, New York, United States
Site US10044
🇺🇸Middleburg Heights, Ohio, United States
Site US10040
🇺🇸Virginia Beach, Virginia, United States
Site US10012
🇺🇸Myrtle Beach, South Carolina, United States
Site US10046
🇺🇸Dallas, Texas, United States
Site US10004
🇺🇸Dallas, Texas, United States
Site US10013
🇺🇸Seattle, Washington, United States
Site US10002
🇺🇸Burien, Washington, United States
Site US10028
🇺🇸Wenatchee, Washington, United States
Site AR54002
🇦🇷Rosario, Santa Fe, Argentina
Site AR54007
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Site AU61007
🇦🇺St Leonards, New South Wales, Australia
Site AU61001
🇦🇺Woodville South, South Australia, Australia
Site AU61008
🇦🇺St. Albans, Victoria, Australia
Site AU61015
🇦🇺Clayton, Victoria, Australia
Site BE32001
🇧🇪Mons, Hainaut, Belgium
Site AU61017
🇦🇺Parkville, Victoria, Australia
Site BE32008
🇧🇪Liege, Belgium
Site BE32007
🇧🇪Yvoir, Belgium
Site CA15003
🇨🇦Kelowna, British Columbia, Canada
Site CA15022
🇨🇦Kelowna, British Columbia, Canada
Site CA15013
🇨🇦Oakville, Ontario, Canada
Site CL56002
🇨🇱Temuco, IX Region, Chile
Site CA15023
🇨🇦Granby, Quebec, Canada
Site CA15004
🇨🇦Montreal, Quebec, Canada
Site CL56001
🇨🇱Santiago, RM, Chile
Site DK45008
🇩🇰Holstebro, Midtjylland, Denmark
Site DK45001
🇩🇰Odense C, Denmark
Site DK45003
🇩🇰Herlev, Denmark
Site FI35804
🇫🇮Pori, Länsi-Suomen Lääni, Finland
Site FI35803
🇫🇮Seinäjoki, Länsi-Suomen Lääni, Finland
Site FI35806
🇫🇮Pietarsaari, Finland
Site FR33007
🇫🇷Lyon Cedex 3, France
Site FR33003
🇫🇷Creteil, Val-de-Marne, France
Site FR33006
🇫🇷Bordeaux, France
Site FR33005
🇫🇷La Roche sur Yon, France
Site FR33014
🇫🇷Caen Cedex 05, France
Site FR33015
🇫🇷Le Mans Cedex 2, France
Site FR33012
🇫🇷Lille Cedex, France
Site FR33011
🇫🇷Nimes, France
Site FR33013
🇫🇷Saint Mande, France
Site FR33009
🇫🇷Quimper, France
Site FR33001
🇫🇷Pierre Benite, France
Site DE49004
🇩🇪Nürtingen, Baden-Württemberg, Germany
Site DE49002
🇩🇪Freiburg, Baden-Württemberg, Germany
Site DE49005
🇩🇪Bonn, Germany
Site IL97201
🇮🇱Kfar-Saba, HaMerkaz, Israel
Site DE49014
🇩🇪Hamburg, Germany
Site IL97211
🇮🇱Zerifin, HaMerkaz, Israel
Site IL97202
🇮🇱Haifa, Israel
Site IL97205
🇮🇱Haifa, Israel
Site IT39003
🇮🇹Milano, Lombardia, Italy
Site IT39005
🇮🇹Meldola, Emilia-Romagna, Italy
Site IT39012
🇮🇹Milano, Lombardia, Italy
Site IT39007
🇮🇹Novara, Piemonte, Italy
Site IT39008
🇮🇹Pisa, Toscana, Italy
Site IT39011
🇮🇹Trento, Trentino-Alto Adige, Italy
Site IT39006
🇮🇹Padova, Veneto, Italy
Site JP81007
🇯🇵Yokohama, Kanagawa, Japan
Site JP81008
🇯🇵Kyoto, Japan
Site KR82004
🇰🇷Incheon, Korea, Republic of
Site KR82001
🇰🇷Seoul, Korea, Republic of
Site NL31002
🇳🇱Sneek, Friesland, Netherlands
Site NL31005
🇳🇱Eindhoven, Noord-Brabant, Netherlands
Site NL31007
🇳🇱Nijmegen, Gelderland, Netherlands
Site NL31008
🇳🇱Amsterdam, Noord-Holland, Netherlands
Site NZ64008
🇳🇿Kensington, Northland, New Zealand
Site NL31009
🇳🇱Zwolle, Overijssel, Netherlands
Site NL31006
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Site NZ64002
🇳🇿Dunedin, South Island, New Zealand
Site NZ64005
🇳🇿Nelson, Tasman District, New Zealand
Site PL48003
🇵🇱Wroclaw, Dolnoslaskie, Poland
Site PL48007
🇵🇱Krakow, Malopolskie, Poland
Site RO40008
🇷🇴Cluj-Napoca, Cluj, Romania
Site PL48005
🇵🇱Gdańsk, Pomerania, Poland
Site PL48010
🇵🇱Slupsk, Pomorskie, Poland
Site PL48001
🇵🇱Myslowice, Poland
Site RO40002
🇷🇴Floresti, Cluj, Romania
Site RO40003
🇷🇴Bucharest, Romania
Site RO40009
🇷🇴Cluj-Napoca, Cluj, Romania
Site RO40011
🇷🇴Timisoara, Timis, Romania
Site RU70001
🇷🇺Moscow, Russian Federation
Site RU70003
🇷🇺Moscow, Russian Federation
Site RO40006
🇷🇴Bucharest, Romania
Site RU70013
🇷🇺Ivanovo, Russian Federation
Site RU70007
🇷🇺St. Petersburg, Russian Federation
Site RU70006
🇷🇺Omsk, Russian Federation
Site RU70005
🇷🇺Penza, Russian Federation
Site RU70014
🇷🇺Moscow, Russian Federation
Site SK42106
🇸🇰Žilina, Slovakia
Site ES34012
🇪🇸Barcelona, Cataluña, Spain
Site ES34010
🇪🇸Sabadell, Barcelona, Spain
Site SE46006
🇸🇪Stockholm, Sodermanlands Lan, Sweden
Site SE46002
🇸🇪Örebro, Orebro Län, Sweden
Site ES34019
🇪🇸Madrid, Spain
Site ES34004
🇪🇸Madrid, Spain
Site SE46001
🇸🇪Malmö, Skåne Län, Sweden
Site SE46007
🇸🇪Goteborg, Vastra Gotalands Lan, Sweden
Site TW88607
🇨🇳Taoyuan, Taiwan
Site TW88605
🇨🇳Taipei, Taiwan
Site US10026
🇺🇸Santa Rosa, California, United States
Site AU61013
🇦🇺Waratah, New South Wales, Australia
Site KR82008
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Site IL97206
🇮🇱Jerusalem, Israel
Site CL56004
🇨🇱Reñaca, Viña Del Mar, Chile
Site FI35801
🇫🇮Tampere, Oulun Laani, Finland
Site PL48011
🇵🇱Warszawa, Mazowieckie, Poland
Site CL56007
🇨🇱Providencia, Santiago, Chile
Site CL56005
🇨🇱Viña Del Mar, Valparaiso, Chile
Site FI35807
🇫🇮Turku, Finland
Site SK42102
🇸🇰Michalovce, Slovakia
Site ES34020
🇪🇸Oviedo, Asturias, Spain
Site CA15024
🇨🇦Abbotsford, British Columbia, Canada
Site TW88601
🇨🇳Kaohsiung, Taiwan
Site BE32005
🇧🇪Kortrijk, West-Vlaanderen, Belgium