MedPath

A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations

Phase 3
Terminated
Conditions
Non-small Cell Lung Cancer (NSCLC)
Interventions
Registration Number
NCT02588261
Lead Sponsor
Astellas Pharma Global Development, Inc.
Brief Summary

The purpose of the study was to evaluate the progression free survival (PFS), based on independent radiologic review (IRR), of ASP8273 compared to erlotinib or gefitinib in patients with locally advanced, metastatic or unresectable stage IIIB/IV adenocarcinoma non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations.

This study also assessed Overall survival (OS); Overall response rate (ORR) as assessed by IRR; PFS as assessed by the investigator; Disease control rate (DCR) as assessed by IRR; Duration of Response (DOR) by IRR; Safety of ASP8273; and Quality of Life (QOL) and patient-reported outcome (PRO) parameters.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
530
Inclusion Criteria
  • Subject agrees not to participate in another interventional study while on treatment.

  • Female subject must either:

    • Be of nonchildbearing potential: postmenopausal (defined as at least 1 year without any menses) prior to Screening, or documented surgically sterile
    • Or, if of childbearing potential: Agree not to try to become pregnant during the study and for 28 days after the final study drug administration; And have a negative serum pregnancy test at Screening; And, if heterosexually active, agree to consistently use 2 forms of highly effective birth control (at least 1 of which must be a highly effective method and one must be a barrier method) starting at Screening and throughout the study period and for 28 days after the final study drug administration.
  • Female subject must not be breastfeeding at Screening or during the study period, and for 28 days after the final study drug administration.

  • Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.

  • Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.

  • Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after the final study drug administration.

  • Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

  • Subject has histologically confirmed locally advanced, metastatic or unresectable Stage IIIB/IV adenocarcinoma NSCLC (newly diagnosed or recurrent). Subjects with mixed histology are eligible if adenocarcinoma is the predominant histology.

  • Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.

  • Subject must meet all of the following criteria on the laboratory tests that will be analyzed centrally within 7 days prior to the first dose of study drug. In case of multiple laboratory data within this period, the most recent data should be used.

    • Neutrophil count > 1,000/mm3
    • Platelet count ≥ 7.5 x 104 /mm3
    • Hemoglobin > 8.0 g/dL
    • Serum creatinine ˂ 2.0 x upper limit of normal (ULN) or an estimated glomerular filtration rate (eGFR) of > 50 mL/min as calculated by the Cockcroft Gault Method
    • Total bilirubin ˂1.5 x ULN (except for subjects with documented Gilbert's syndrome)
    • AST and ALT ˂ 3.0 x ULN or ≤ 5 x ULN if subject has documented liver metastases
    • Serum sodium level is ≥ 130 mmol/L
  • Subject has an EGFR activating mutation (exon 19 deletion or exon 21 L858R), with or without T790M mutation, by local or central testing on examination of a NSCLC FFPE specimen (archival or fresh biopsy). Subjects harboring both exon 19 deletion and exon 21 L858R mutations are not eligible. A tissue sample from the same block used to determine eligibility by local testing should be available to send to the central lab for confirmatory testing. Subjects randomized based on local results indicating presence of EGFR mutation may remain on study if central results are discordant.

  • Subject must have at least 1 measureable lesion based on RECIST V1.1. Previously irradiated lesions will not be considered as measurable lesions.

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Exclusion Criteria
  • Subject has received intervening anticancer treatment or previous treatment with chemotherapy for metastatic disease other than palliative local radiation to painful bone metastases completed at least 1 week prior to the first dose of study drug. The administration of neoadjuvant or adjuvant chemotherapy is allowed as long as it has finalized ≥ 6 months before the first dose of study drug.
  • Subject has received a prior treatment with a therapeutic agent targeting EGFR (e.g., afatinib, dacomitinib, ASP8273, etc).
  • Subject has received investigational therapy within 28 days or 5 half-lives prior to the first dose of study drug.
  • Subject has received radiotherapy within 1 week prior to the first dose of study drug. If the subject received radiotherapy > 1 week prior to study treatment, the irradiated lesion cannot be the only lesion used for evaluating response.
  • Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy, does not have brain metastasis related symptoms, is not requiring systemic steroids for at least 2 weeks prior to study drug administration, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 2 weeks prior to study drug administration. Steroid inhaler use or ointment treatment for other concomitant medical disease is permitted.
  • Subject has received blood transfusions or hematopoietic factor therapy within 14 days prior to the first dose of study drug.
  • Subject has had a major surgical procedure (other than a biopsy) within 14 days prior to the first dose of study drug, or one is planned during the course of the study.
  • Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection.
  • Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP8273, erlotinib or gefitinib.
  • Subject has evidence of an active infection requiring systemic therapy within 14 days prior to the planned first dose of study drug.
  • Subject has severe or uncontrolled systemic diseases including uncontrolled hypertension (blood pressure > 150/100 mmHg) or active bleeding diatheses.
  • Subject has history of drug-induced interstitial lung disease (ILD) or any evidence of active ILD.
  • Subject has ongoing cardiac arrhythmia that is Grade ≥ 2 or uncontrolled atrial fibrillation of any grade.
  • Subject currently has Class 3 or 4 New York Heart Association congestive heart failure.
  • Subject has history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months prior to the planned first dose of study drug.
  • Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.
  • Subject has concurrent corneal disorder or any ophthalmologic condition which, in the investigator's opinion, makes the subject unsuitable for study participation (i.e., advanced cataracts, glaucoma).
  • Subject has difficulty taking oral medication or any digestive tract dysfunction or inflammatory bowel disease that would interfere with the intestinal absorption of drug.
  • Subject has another past or active malignancy which requires treatment. Prior carcinoma in situ or non-melanoma skin cancer after curative resection are permitted.
  • Subject has any condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
  • Subject has received potent CYP 3A4 inhibitors within 7 days prior to first dose of study drug or proton pump inhibitors such as omeprazole within 14 days prior to first dose of study drug.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ASP8273naquotinib mesilateParticipants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
erlotinib or gefitinibErlotinibParticipants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
erlotinib or gefitinibGefitinibParticipants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) as Assessed by Independent Radiologic Review (IRR)From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by IRR. Results are based Kaplan-Meier estimate. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available.

Secondary Outcome Measures
NameTimeMethod
Percentage of DeathsFrom date of randomization up to data cut-off date 21 Dec 2017 (approximately 22 months)

All events of death after the first study drug administration were included.

Percentage of Participants With Objective Response (OR)From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)

Percentage of participants with OR was defined as the proportion of participants with best overall response as complete response (CR) or partial response (PR) without confirmation based on the RECIST v1.1 as assessed by the blinded IRR. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

PFS as Assessed by the InvestigatorFrom date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)

PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on RECIST V1.1, as assessed by local investigator. Results are based Kaplan-Meier estimate. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available.

Percentage of Participants With Disease ControlFrom date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months)

Percentage of participants with disease control was defined as the proportion of participants whose best overall response was rated as CR, PR or stable disease (SD) among all analyzed participants based on RECIST V1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug.

Duration of Response (DOR)From date of first response up to data cut-off date 09 May 2017 (approximately 15 months)

DOR was defined as the time from the date of the first response CR/PR (whichever was first recorded) as assessed by IRR to the date of radiographical progression or date of censoring. If a participant had not progressed, the participant was censored at the date of last radiological assessment or at the date of first CR/PR if no post-baseline radiological assessment was available. Results are based Kaplan-Meier estimate.

Number of Participants With Adverse Events (AEs)From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 09 May 2017

Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.

Functional Assessment of Cancer Therapy - EGFR Inhibitors Subscale (FACT-EGFRI-18) QuestionnaireDay 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

ACT-EGFRI-18 is an 18-item Likert-scaled questionnaire, used to assess the effect of EGFR inhibitors on quality of life (QoL). The questionnaire is arranged in three HRQL dimensions: physical (seven items), social/emotional (six items), and functional well-being (five items). The response scores ranged from 0 to 4, and the response categories include "not at all", "a little bit", "somewhat", "quite a bit", and "very much." Negatively worded items (e.g., "My skin bleeds easily "or "My skin condition affects my mood") are reverse-scored, so that participants who experience a higher impact of symptom burden on HRQL receive a lower score (range 0-72).

European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC-QLQ-LC13)Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

The EORTC-QLQ-LC13 is a validated module of the EORTC-QLQ-Core 30, which includes module items that evaluate symptoms such as cough, hemoptysis, shortness of breath, sore mouth or tongue, dysphagia, tingling hands or feet, hair loss and pain. The total score for the questionnaire ranges from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.

European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30)Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

EORTC-QLQ-LC30 is a 30-item cancer-specific questionnaire with multitrait scaling was used to create five functional domain scales: Physical, Role, Emotional, Social and Cognitive; two items evaluate global QoL; in addition, three symptom scales assess Fatigue, Pain and Emesis; and six single items assess other symptoms. The total score ranges from 0 to 100, with a high score for a functional scale representing a high/healthy level of functioning and a high score for a symptom scale or item representing a high level of symptomatology or problems.

EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L)Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months)

The EQ-5D is a generic preference-based measure that indirectly measures the utility for health that generates an index-based summary score based upon societal preference weights. The EQ-5D-5L consists of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale (VAS) for health status. Each item has 5 response levels ranging from level 1 (no problem or none) to level 5 (unable to perform activity). The VAS ranges from 0 (worst health status) and 100 (best health status).

Trial Locations

Locations (167)

Site US10025

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Fountain Valley, California, United States

Site US10003

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Santa Monica, California, United States

Site US10013

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Aventura, Florida, United States

Site US10037

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Scarborough, Maine, United States

Site US10033

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Los Angeles, California, United States

Site US10050

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Atlanta, Georgia, United States

Site UA38009

🇺🇦

Uzhgorod, Zakarpats'ka Oblast', Ukraine

Site AU61002

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Fitzroy, Victoria, Australia

Site CL56001

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Santiago, Región Metropolitana De Santia, Chile

Site US10012

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Mount Kisco, New York, United States

Site US10027

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Rochester, Minnesota, United States

Site DE49006

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Wurzburg, Bayern, Germany

Site AU61003

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Randwick, New South Wales, Australia

Site US10018

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Whittier, California, United States

Site US10031

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Oxnard, California, United States

Site IT39013

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Lucca, Italy

Site CL56002

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Vina del Mar, Valparaíso, Chile

Site FR33007

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Pierre Benite, Rhône, France

Site BE32002

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Gent, West-Vlaanderen, Belgium

Site IT39012

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Piacenza, Italy

Site JP81024

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Kobe, Hyogo, Japan

Site DE49003

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Gauting, Bayern, Germany

Site CL56007

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Vina del Mar, Valparaíso, Chile

Site FR33011

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Suresnes, Hauts-de-Seine, France

Site FR33006

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Grenoble, Isère, France

Site JP81005

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Miyakojima-ku, Osaka, Japan

Site KR82004

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Suwon-si, Gyeonggi-do, Korea, Republic of

Site US10011

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Lacey, Washington, United States

Site JP81008

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Kurume, Hukuoka, Japan

Site AU61007

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Woolloongabba, Queensland, Australia

Site KR82016

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Suwon-si, Gyeonggido [Kyonggi-do], Korea, Republic of

Site DE49007

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Kassel, Hessen, Germany

Site US10048

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Saint Petersburg, Florida, United States

Site DE49005

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Karlsruhe, Baden-Württemberg, Germany

Site AU61005

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Adelaide, South Australia, Australia

Site CA15006

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Toronto, Ontario, Canada

Site FR33010

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Pessac, Gironde, France

Site HU36006

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Szombathely, Vas, Hungary

Site JP81018

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Matsuyama, Ehime, Japan

Site IT39009

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Rozzano, Lombardia, Italy

Site JP81006

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Okayama, Japan

Site NL31006

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Alkmaar, Noord-Holland, Netherlands

Site IT39004

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Monza, Lombardia, Italy

Site FR33003

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Creteil, Ilej-de-France, France

Site KR82013

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Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of

Site US10046

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Milwaukee, Wisconsin, United States

Site AU61008

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East Melbourne, Victoria, Australia

Site DE49008

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Freiburg, Baden-Württemberg, Germany

Site JP81013

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Hiroshima, Hirosima [Hiroshima], Japan

Site PT35104

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Lisbon, Lisboa, Portugal

Site RO40004

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Floresti, Cluj, Romania

Site IT39015

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Brescia, Italy

Site JP81004

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Tokyo, Tôkyô [Tokyo], Japan

Site JP81001

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Sunto-gun, Sizuoka [Shizuoka], Japan

Site PE51004

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San Isidro, Lima, Peru

Site JP81002

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Osaka-sayama, Ôsaka [Osaka], Japan

Site KR82009

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Jinju-si, Gyeongsangnamdo, Korea, Republic of

Site KR82011

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Ulsan, Ulsan Gwang'yeogsi, Korea, Republic of

Site SG65001

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Singapore, Central Singapore, Singapore

Site RO40001

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Craiova, Dolj, Romania

Site RO40010

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Craiova, Dolj, Romania

Site TW88601

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Tainan, Taiwan

Site UA38005

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Kryvyi Rih, Dnipropetrovs'ka Oblast', Ukraine

Site KR82006

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Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of

Site RU70017

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Ufa, Bashkortostan, Russian Federation

Site PE51001

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Cercado De Lima, Arequipa, Peru

Site PT35103

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Coimbra, Portugal

Site ES34017

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Valencia, Spain

Site KR82003

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Jeonju, Jeonrabugdo[Chollabuk-do], Korea, Republic of

Site ES34005

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Sevilla, Spain

Site ES34016

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Madrid, Spain

Site TH66001

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Bangkok, Krung Thep Maha Nakhon [Bangkok], Thailand

Site UA38001

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Dnipropetrovsk, Dnipropetrovs'ka Oblast', Ukraine

Site RU70001

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Saint Petersburg, Russian Federation

Site TW88605

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Taichung City, Taichung, Taiwan

Site ES34003

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Barcelona, Catalunya, Spain

Site RO40012

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Bucuresti, Romania

Site ES34010

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Malaga, Málaga, Spain

Site UA38008

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Ivano-Frankivsk, Ivano-Frankivs'ka Oblast', Ukraine

Site ES34008

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San Sebastian, Guipuzcoa, Guipúzcoa, Spain

Site TW88603

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Taichung, Taiwan

Site TH66012

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Bangkok, Krung Thep Maha Nakhon [Bangkok], Thailand

Site ES34004

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Ourense, Spain

Site TW88609

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Taipei, Taiwan

Site TH66006

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Songkla, Thailand

Site US10034

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Boston, Massachusetts, United States

Site US10030

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Minneapolis, Minnesota, United States

Site TW88607

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Taoyuan Hsien, Taoyuan, Taiwan

Site HU36001

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Budapest, Hungary

Site MY60001

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Kuantan Pahang, Pahang, Malaysia

Site FR33004

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Tours, Indre-et-Loire, France

Site FR33009

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Saint Priest en Jarez, Loire, France

Site RO40008

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Timisoara, Timis, Romania

Site TH66002

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Chiang Rai, Thailand

Site TH66004

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Khon Kaen, Thailand

Site GB44001

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Liverpool, Wirral, United Kingdom

Site HU36003

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Tatabanya, Tatabánya, Hungary

Site MY60002

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Georgetown, Pulau Pinang, Malaysia

Site HU36007

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Budapest, Hungary

Site HU36002

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Szekesfehervar, Fejér, Hungary

Site PT35101

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Amadora, Lisboa, Portugal

Site HU36004

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Farkasgyepu, Veszprém, Hungary

Site PE51008

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Miraflores, Lima, Peru

Site PT35102

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Lisboa, Portugal

Site MY60004

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Kuching, Sarawak, Malaysia

Site RO40006

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Sibiu, Romania

Site SG65002

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Singapore, Central Singapore, Singapore

Site TW88604

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Tainan, Taiwan

Site GB44002

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Middlesex, Hertfordshire, United Kingdom

Site NL31001

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Arnhem, Gelderland, Netherlands

Site TH66011

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Chom Thong, Chiang Mai, Thailand

Site US10009

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Nashville, Tennessee, United States

Site US10023

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Nashville, Tennessee, United States

Site IT39003

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Bergamo, Italy

Site IT39002

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Cremona, Italy

Site IT39014

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Milano, Italy

Site JP81017

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Osakasayama-shi, Hukuoka [Fukuoka], Japan

Site JP81012

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Sendai, Miyagi, Japan

Site JP81022

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Niigata, Japan

Site JP81020

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Osakasayama-shi, Osaka, Japan

Site ES34006

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Madrid, Spain

Site ES34015

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Valencia, Spain

Site IT39008

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Roma, Italy

Site ES34002

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Valencia, Spain

Site US10036

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La Jolla, California, United States

Site US10029

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Beverly Hills, California, United States

Site US10051

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Loma Linda, California, United States

Site US10052

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Redondo Beach, California, United States

Site US10042

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Baton Rouge, Louisiana, United States

Site US10047

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Glenwood Springs, Colorado, United States

Site US10045

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Albuquerque, New Mexico, United States

Site US10021

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Bethlehem, Pennsylvania, United States

Site AU61004

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Footscray, Victoria, Australia

Site CA15002

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Montreal, Quebec, Canada

Site FR33012

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Bayonne, Pyrénées-Atlantiques, France

Site DE49004

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Köln, Nordrhein-Westfalen, Germany

Site IT39011

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Aviano, Pordenone, Italy

Site JP81015

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Kanazawa, Isikawa [Ishikawa], Japan

Site JP81014

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Sapporo, Hokkaidô, Japan

Site JP81016

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Kurashiki, Okayama, Japan

Site JP81021

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Hirakata, Ôsaka [Osaka], Japan

Site JP81010

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Yokohama, Kanagawa, Japan

Site JP81019

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Sunto-gun, Shizuoka, Japan

Site KR82005

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Cheongiu, Chungcheongbugdo, Korea, Republic of

Site JP81023

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Wakayama, Japan

Site KR82017

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Bundang, Gyeonggido, Korea, Republic of

Site KR82008

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Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of

Site KR82002

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Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of

Site KR82007

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Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of

Site KR82015

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Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of

Site KR82010

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Busan Gwang'yeogsi, Korea, Republic of

Site RO40007

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Ploiesti, Prahova, Romania

Site RU70012

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Arkhangelsk, Arkhangel'skaya Oblast', Russian Federation

Site RU70016

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Nalchik, Kabardino-Balkarskaya Respublika, Russian Federation

Site RU70009

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Magnitogorsk, Chelyabinskaya Oblast', Russian Federation

Site RU70008

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Pyatigorsk, Stavropol'skiy Kray, Russian Federation

Site TW88606

🇨🇳

Kaohsiung, Taiwan

Site TW88608

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Taipei, Taiwan

Site TW88611

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Taipei, Taiwan

Site UA38006

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Chernivtsi, Chernivets'ka Oblast', Ukraine

Site JP81025

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Yokohama, Kanagawa, Japan

Site KR82001

🇰🇷

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of

Site KR82014

🇰🇷

Seoul, Seoul Teugbyeolsi, Korea, Republic of

Site GB44003

🇬🇧

Sheffield, United Kingdom

Site UA38007

🇺🇦

Lutsk, Volyns'ka Oblast', Ukraine

Site UA38004

🇺🇦

Lviv, L'vivs'ka Oblast', Ukraine

Site UA38003

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Uzhgorod, Zakarpats'ka Oblast', Ukraine

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