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NCT06952803PHASE3Recruiting

A Study of Metastases Free Survival With Saruparib vs Placebo Added to a Standard RT/ADT in Men With High-risk Prostate Cancer With a BRCA Mutation

AstraZeneca

Start Date

8/6/2025

Completion Date

4/30/2036

Summary

The purpose of the study is to demonstrate superiority of Saruparib (AZD5305) relative to placebo added to a standard radiation therapy (RT) + androgen deprivation therapy (ADT) regimen by assessment of metastases-free survival in participants with high-risk and very high-risk localised/locally advanced prostate cancer with a breast cancer gene mutation (BRCAm).

Detailed Description

Approximately, 700 adult participants with localised/locally advanced prostate cancer will be randomized in a 1:1 ratio to receive saruparib or placebo with ADT (+ abiraterone) in one of the following two cohorts: Cohort A: 400 adult participants with newly diagnosed high-risk and very high-risk (localised/locally advanced) prostate cancer who have received primary RT and are receiving continuous ADT, and participants with high-risk biochemical recurrence (BCR) \[including prostate-specific antigen (PSA) persistence\] following a radical prostatectomy who have received salvage RT are receiving continuous ADT. Cohort B: 300 adult participants with newly diagnosed very high-risk (locally advanced) prostate cancer who have received primary RT and who are receiving continuous ADT and abiraterone. All participants will be followed for survival until the end of the study. Independent data monitoring committee (DMC) composed of experts will be convened to confirm the safety and efficacy of Saruparib + ADT (+ abiraterone).

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Male participants with a histologically documented diagnosis of prostate adenocarcinoma. * Newly diagnosed high-risk and very high-risk (localised/locally advanced) prostate cancer or a high-risk biochemical recurrence (BCR) following radical prostatectomy. * Provision of a formalin fixed and paraffin embedded (FFPE) tumour tissue sample. * Confirmed BRCA1 or BRCA2 mutation status by central tumour tissue is required for enrolment. * Participants required to have a computed tomography (CT) or magnetic resonance imaging (MRI) and a bone scan following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0). * Participants required to have a prostate-specific membrane antigen-positron emission tomography (PSMA-PET) following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0). * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomization. * Minimum life expectancy of 12 months. * Adequate organ and bone marrow function as described in study protocol. * All participants will have received either primary or salvage RT. Participants must be eligible for randomisation within 10 months of initial diagnosis (de novo or BCR). Radiotherapy administered to the prostate (± pelvis) either in the primary or salvage setting must be delivered with curative intent. Use of metastases-directed therapy, as part of the RT radiation plan, is permitted as localised RT treatment for a metastatic lesion(s) outside the pelvis. * All participants will have received a planned regimen of ADT with a gonadotropin releasing hormone (GnRH) analogue. * Participants must not father children or donate sperm from signing informed consent form (ICF), during the study intervention and for 6 months after the last dose of study intervention. * Participants must use a condom (with spermicide - where permitted) from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners. Exclusion Criteria: * Participants with a history of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or with features suggestive of MDS/AML. * Participants with any known predisposition to bleeding \[e.g., active peptic ulceration, recent (within 6 months) hemorrhagic stroke, proliferative diabetic retinopathy\]. * Any history of persisting (\> 2 weeks) severe cytopenia due to any cause. * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib and/or abiraterone. * History of another primary malignancy, with exceptions. * Persistent toxicities \[Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2\] caused by previous anticancer therapy. * Cardiac criteria, including history of arrhythmia and cardiovascular disease. * Evidence of active and uncontrolled hepatitis B and/or hepatitis C. * Evidence of active and uncontrolled human immunodeficiency virus (HIV) infection. * Active tuberculosis infection. * Any prior chemotherapy (i.e., docetaxel) or immunotherapy; any prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor. * Prior treatment within 14 days with blood product support or growth factor support. * Concomitant use of strong inducers and inhibitors of CYP3A4 (applies to saruparib and abiraterone) or herbal supplements within 21 days or at least 5 half-lives (whichever is longer), of randomization. * Concomitant use of drugs that are known to prolong QT and have a known risk of Torsades de Pointes (TdP). * Participants with a known hypersensitivity to saruparib or any excipients of these products.

Interventions

DRUG

Saruparib

DRUG

Placebo

DRUG

Abiraterone + Prednisolone/Prednisone

DRUG

Androgen Deprivation Therapy (ADT)

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Conditions

Prostate Cancer

Locations

Research Site

Phoenix, Arizona 85054

United States

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Tucson, Arizona 85741

United States

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La Jolla, California 92037

United States

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La Jolla, California 92093

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Los Angeles, California 90048

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San Diego, California 92123

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San Luis Obispo, California 93401

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Lakewood, Colorado 80215

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Hialeah, Florida 33016

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Jacksonville, Florida 32224

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Tallahassee, Florida 32308

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Tampa, Florida 33612

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Newnan, Georgia 30265

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Chicago, Illinois 60611

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Chicago Ridge, Illinois 60415

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Lake Barrington, Illinois 60010

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Greenwood, Indiana 46143

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Jeffersonville, Indiana 47130

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Bethesda, Maryland 20817

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Towson, Maryland 21204

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Plymouth, Massachusetts 02360

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Rochester, Minnesota 55905

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Hackensack, New Jersey 07601

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Voorhees Township, New Jersey 08043

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Albany, New York 12206

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New York, New York 10065

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Syracuse, New York 13210

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Columbus, Ohio 43230

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Springfield, Oregon 97477

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Hershey, Pennsylvania 17033

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Lancaster, Pennsylvania 17601

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Pittsburgh, Pennsylvania 15212

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Providence, Rhode Island 02903

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Myrtle Beach, South Carolina 29572

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Nashville, Tennessee 37209

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Austin, Texas 78705

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Austin, Texas 78745

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Houston, Texas 77074

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San Antonio, Texas 78229

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Spring, Texas 77380

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Salt Lake City, Utah 84112

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Norfolk, Virginia 23502

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Roanoke, Virginia 24014

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Virginia Beach, Virginia 23462

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Seattle, Washington 98109

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CABA, 1426

Argentina

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CABA, C1113AAE

Argentina

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Ciudad de Buenos Aires, 1181

Argentina

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Ciudad de Buenos Aires, 1426

Argentina

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Ciudad de Buenos Aires, C1419AHL

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Córdoba, 5000

Argentina

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Córdoba, X5008HHW

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Cuidad Autónoma de Buenos Aire, C1426ANZ

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La Plata, 1900

Argentina

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Pergamino, B2700CPM

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Rosario, S2000KZE

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San Miguel de Tucumán, 4000

Argentina

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Viedma, R8500ACE

Argentina

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Kingswood, 2747

Australia

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Murdoch, 6150

Australia

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Orange, 2800

Australia

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South Brisbane, 4101

Australia

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St Leonards, 2065

Australia

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Waratah, 2298

Australia

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Woolloongabba, 4102

Australia

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Graz, 8036

Austria

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Innsbruck, 6020

Austria

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Linz, 4020

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Vienna, 1020

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Vienna, 1090

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Brussels, 1070

Belgium

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Brussels, 1200

Belgium

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Ghent, 9000

Belgium

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Jette, 1090

Belgium

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Kortrijk, 8500

Belgium

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Leuven, 3000

Belgium

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Libramont-Chevigny, 6800

Belgium

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Roeselare, 8800

Belgium

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Wilrijk, 2610

Belgium

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Cachoeiro de Itapemirim, 29308-014

Brazil

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Curitiba, 80810-050

Brazil

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Curitiba,

Brazil

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Jaú, 17210-120

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Londrina, 86015-520

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Pelotas, 96020-080

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Porto Alegre, 90035-000

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Porto Alegre, 91350200

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Rio de Janeiro, 22.250-905

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Rio de Janeiro, 22775-001

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Salvador, 41950640

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São Paulo, 01246-000

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São Paulo, 01327-001

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Calgary, Alberta T2V 1P9

Canada

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Abbotsford British Columbia, British Columbia V2S 0C2

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Vancouver, British Columbia V5Z 4E6

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Barrie, Ontario L4M 6M2

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Brampton, Ontario L6R 3J7

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London, Ontario N6A 5A5

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Toronto, Ontario M5G 2M9

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Chicoutimi, Quebec G7H 7K9

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Montreal, Quebec H3T 1E2

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Saskatoon, Saskatchewan S7N 4H4

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Toronto, M4N 3M5

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Concepción, 4070196

Chile

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La Serena, 1720430

Chile

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Temuco, 4781156

Chile

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Beijing, 100020

China

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Beijing, 100021

China

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Beijing, 100176

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Changchun, 130012

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Changsha, 410013

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Chongqing, 400016

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Guangzhou, 510060

China

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Guangzhou, 510080

China

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Guangzhou, 510180

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Guangzhou, 510280

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Hangzhou, 31000

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Hangzhou, 310022

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Jinan, 250021

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Jinhua, 322100

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Lanzhou, 730030

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Nanchang, 330006

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Ningbo, 315010

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Shanghai, 200025

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Shanghai, 20032

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Shenyang, 110001

China

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Shenyang, 110042

China

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Sichuan, 610041

China

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Suining, 629018

China

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Tianjin, 300201

China

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Wuhan, 430022

China

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Wuhan, 430060

China

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Wuhu, 241000

China

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Xiamen, 361003

China

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Yangzhou, 225001

China

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Zhuhai, 519099

China

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Helsinki, 00290

Finland

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Helsinki, FI-00180

Finland

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Kuopio, 70210

Finland

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Oulu, 90029

Finland

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Tampere, FI-33521

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Turku, 20520

Finland

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Angers, 49100

France

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Bordeaux, 33000

France

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Caen, 14076

France

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Clermont-Ferrand, 63011

France

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Le Mans, 72000

France

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Marseille, 13273

France

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Montpellier, 34070

France

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Montpellier, 34298

France

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Nice, 06100

France

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Nîmes, 30029

France

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Paris, 75020

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Paris, 75674

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Paris, 75970

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Pierre-Bénite, 69310

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Rennes, 35000

France

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Saint-Herblain, 44805

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Saint-Priest-en-Jarez, 42270

France

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Strasbourg, 67200

France

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Suresnes, 92151

France

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Tours, 37044

France

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Vandœuvre-lès-Nancy, 54511

France

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Villejuif, 94805

France

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Augsburg, 86156

Germany

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Berlin, 10117

Germany

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Braunschweig, 38126

Germany

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Cologne, 50937

Germany

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Dresden, 1307

Germany

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Duisburg, 47169

Germany

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Düsseldorf, 40226

Germany

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Essen, 45147

Germany

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Giessen, 35392

Germany

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Göttingen, 37075

Germany

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Gronau, 48599

Germany

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Hamburg, 20246

Germany

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Herne, 44625

Germany

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Kiel, 24105

Germany

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Lübeck, 23538

Germany

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Marburg, 35043

Germany

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Münster, 48149

Germany

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Nuremberg, 90419

Germany

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Nürtingen, 72622

Germany

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Regensburg, 93053

Germany

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Schwerin, 19049

Germany

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Trier, 54292

Germany

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Ulm, 89081

Germany

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Würzburg, 97080

Germany

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Budapest, 1082

Hungary

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Budapest, 1122

Hungary

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Budapest, H-1145

Hungary

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Debrecen, 4032

Hungary

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Győr, 9024

Hungary

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Gyula, 5700

Hungary

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Zalaegerszeg, 8900

Hungary

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Ansārinagar, 110 029

India

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Babgalore, 560069

India

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Calicut, 673601

India

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Delhi, 110085

India

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Hyderabad, 500019

India

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Kannur, 670103

India

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Kanpur, 208005

India

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Mumbai, 400012

India

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Nagpur, 440001

India

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Varanasi, 221005

India

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Afula, 18101

Israel

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Beersheba, 8410101

Israel

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Haifa, 31096

Israel

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Jerusalem, 91031

Israel

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Jerusalem, 9112001

Israel

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Kfar Saba, 4428164

Israel

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Petah Tikva, 49100

Israel

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Ramat Gan, 52621

Israel

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Tel Aviv, 6423906

Israel

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Arezzo, 52100

Italy

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Bari, 70124

Italy

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Bergamo, 24125

Italy

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Bergamo, 24127

Italy

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Chieti, 66100

Italy

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Genoa, 16132

Italy

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Milan, 20132

Italy

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Milan, 20133

Italy

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Milan, 20141

Italy

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Naples, 80131

Italy

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Palermo, 90127

Italy

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Pisa, 56126

Italy

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Roma, 00144

Italy

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Roma, 00168

Italy

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Rozzano, 20089

Italy

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Torino, 10126

Italy

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Varese, 21100

Italy

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Verona, 37134

Italy

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Bunkyō City, 113-8431

Japan

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Fukuoka, 812-8582

Japan

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Kamakura-shi, 247-8533

Japan

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Kawagoe-shi, 350-8550

Japan

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Kawasaki-shi, 216-8511

Japan

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Kisarazu-shi, 292-8535

Japan

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Kumamoto, 860-8556

Japan

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Kyoto, 606-8507

Japan

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Maebashi, 371-8511

Japan

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Miyazaki, 889-1692

Japan

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Ōta-ku, 373-8550

Japan

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Sagamihara-shi, 252-0375

Japan

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Shimotsuke-shi, 329-0498

Japan

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Yokohama, 232-0024

Japan

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Yokohama, 241-8515

Japan

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Batu Caves, 68100

Malaysia

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Kuala Lumpur, 59100

Malaysia

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Kuala Selangor, 62250

Malaysia

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Pulau Pinang, 10450

Malaysia

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Hilversum, 1213 XZ

Netherlands

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Hoofddorp, 2134 TM

Netherlands

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Maastricht, 6202 AZ

Netherlands

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Nijmegen, 6532 SZ

Netherlands

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Roosendaal, 4708 AE

Netherlands

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Lima, 15036

Peru

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Lima, LIMA 29

Peru

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Lima, Lima 34

Peru

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Trujillo, 13008

Peru

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Gdynia, 81-519

Poland

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Gliwice, 44-101

Poland

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Koszalin, 75-581

Poland

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Krakow, 30-727

Poland

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Piotrkow Trybunalski, 97-300

Poland

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Poznan, 61-731

Poland

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Rzeszów, 35-001

Poland

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Warsaw, 04-073

Poland

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Busan, 49241

South Korea

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Daegu, 41404

South Korea

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Goyang-si, 10408

South Korea

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Seongnam-si, 13620

South Korea

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Seoul, 03080

South Korea

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Seoul, 06273

South Korea

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Seoul, 06351

South Korea

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Seoul, 06591

South Korea

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Seoul, 3722

South Korea

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Seoul, 5505

South Korea

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Barcelona, 08041

Spain

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Barcelona, 8035

Spain

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Girona, 17007

Spain

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Madrid, 28040

Spain

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Madrid, 28041

Spain

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Madrid, 28046

Spain

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Majadahonda, 28222

Spain

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Málaga, 29009

Spain

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Málaga, 29010

Spain

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Oviedo, 33011

Spain

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Sabadell, 08208

Spain

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Santander, 39008

Spain

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Valencia, 46009

Spain

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Valencia, 46014

Spain

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Gothenburg, 413 45

Sweden

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Malmö, 205 02

Sweden

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Stockholm, 112 81

Sweden

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Stockholm, 141 86

Sweden

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Umeå, 901 85

Sweden

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Uppsala, 75185

Sweden

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Kaohsiung City, 83301

Taiwan

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Taichung, 40705

Taiwan

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Taichung, 43503

Taiwan

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Tainan, 704

Taiwan

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Taipei, 10055

Taiwan

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Taipei, 110

Taiwan

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Taipei, 112

Taiwan

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Taoyuan, 333

Taiwan

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Bangkok, 10210

Thailand

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Bangkok, 10400

Thailand

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Bangkok, 10700

Thailand

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Khon Kaen, 40002

Thailand

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Muang, 50200

Thailand

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Pathum Thani, 12120

Thailand

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Songkhla, 90110

Thailand

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Ankara, 06010

Turkey (Türkiye)

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Ankara, 06520

Turkey (Türkiye)

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Ankara, 06620

Turkey (Türkiye)

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Ankara, 06800

Turkey (Türkiye)

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Cordaleo, 35575

Turkey (Türkiye)

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Diyarbakır, 21280

Turkey (Türkiye)

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Istanbul, 34010

Turkey (Türkiye)

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Istanbul, 34098

Turkey (Türkiye)

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Istanbul, 34722

Turkey (Türkiye)

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Izmir, 35040

Turkey (Türkiye)

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Sakarya, 54290

Turkey (Türkiye)

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Seyhan, 01130

Turkey (Türkiye)

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Şahinbey, 27310

Turkey (Türkiye)

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Aberdeen, AB25 2ZN

United Kingdom

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Bristol, BS2 8ED

United Kingdom

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Cambridge, CB2 0QQ

United Kingdom

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Edinburgh, EH4 2XU

United Kingdom

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Exeter, EX2 5DW

United Kingdom

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Glasgow, G12 0YN

United Kingdom

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Greater London, SW3 6JJ

United Kingdom

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Guildford, GU2 7XX

United Kingdom

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London, EC1M6BQ

United Kingdom

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London, NW3 2QG

United Kingdom

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London, WC1N 3BG

United Kingdom

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Manchester, M20 4BX

United Kingdom

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Newcastle, NE7 7DN

United Kingdom

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Plymouth, PL6 8DH

United Kingdom

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Preston, PR2 9HT

United Kingdom

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Romford, RM7 0AG

United Kingdom