A Phase 3, Randomized, Double-blind Study to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Lenvatinib (E7080/MK-7902) Versus Pembrolizumab and Placebo as First Line Treatment for Locally Advanced or Metastatic Urothelial C

Condition: Urothelial Carcinoma

Intervention:

• Biological: Pembrolizumab
• Drug: Lenvatinib
• Drug: Placebo for lenvatinib

Purpose: The purpose of this study is to evaluate the efficacy and safety of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in the treatment of cisplatin-ineligible participants with a Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10, or in participants ineligible for any platinum-containing chemotherapy regardless of CPS, with advanced/unresectable or metastatic urothelial carcinoma (UC). The primary hypotheses for this study are that: 1. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR), and 2. Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Overall Survival (OS).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03898180

Sponsor: Merck Sharp & Dohme Corp.

Primary Outcome Measures:

• Measure: Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
• Time Frame: Up to approximately 40 months
• Safety Issue:
• Measure: Overall Survival (OS)
• Time Frame: Up to approximately 40 months
• Safety Issue:

Secondary Outcome Measures:

• Measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)
• Time Frame: Up to approximately 40 months
• Safety Issue:
• Measure: Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)
• Time Frame: Up to approximately 40 months
• Safety Issue:
• Measure: Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR)
• Time Frame: Up to approximately 40 months
• Safety Issue:
• Measure: Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
• Time Frame: Baseline and up to approximately 40 months
• Safety Issue:
• Measure: Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
• Time Frame: Up to approximately 40 months
• Safety Issue:
• Measure: Number of Participants Who Experience an Adverse Event (AE)
• Time Frame: Up to approximately 40 months
• Safety Issue:
• Measure: Number of Participants Who Discontinue Study Treatment Due to an AE
• Time Frame: Up to approximately 40 months
• Safety Issue:

Estimated Enrollment: 694

Study Start Date: May 6, 2019

Phase: Phase 3

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial carcinoma (UC) of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
• Has ≥1 measurable target lesion per RECIST 1.1 as assessed by the local site investigator/radiologist.
• Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated and adequate for Programmed Death-Ligand 1 (PD-L1) evaluation.
• Has received no prior systemic chemotherapy for advanced or metastatic UC with the following exceptions:
• Neoadjuvant (prior to surgery) platinum-based chemotherapy for treatment of muscle-invasive bladder cancer with recurrence >12 months from completion of the therapy is permitted.
• Adjuvant (following surgery) platinum-based chemotherapy following radical cystectomy, with recurrence >12 months from completion of the therapy, is permitted.
• Meets criteria for either option a or option b (below):
• a. Has a tumor(s) with PD-L1 combined positive score (CPS) ≥10 and is considered ineligible to receive cisplatin-based combination therapy, based on 1 of the following:
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 2 within 7 days prior to randomization
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Grade ≥2 audiometric hearing loss
• NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy OR
• b. In the opinion of the investigator, is considered ineligible to receive any platinum-based chemotherapy (i.e., ineligible for cisplatin and carboplatin) based on:
• ECOG PS of 2 within 7 days prior to randomization. and ≥1 of the following:
• Documented visceral metastatic disease
• NCI CTCAE Version 4.0 Grade ≥2 audiometric hearing loss
• NCI CTCAE Version 4.0 Grade ≥2 peripheral neuropathy
• Other reason for the participant’s being unable to receive both cisplatin and carboplatin safely. Additional criteria for platinum ineligibility will be considered and allowed on a case-by-case basis, following consultation with the Sponsor. Note: Participants considered ineligible for any platinum-based chemotherapy are eligible for this study regardless of their tumor PD-L1 status.
• Has ECOG PS 0, 1, or 2 within 7 days prior to randomization and a life expectancy of ≥3 months.
• Male participants are eligible to participate if they agree to the following during the treatment period and for ≥30 days after the last dose of pembrolizumab or lenvatinib/placebo:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR
• Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below:
• Agrees to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
• A female participant is eligible to participate if she is not pregnant or breastfeeding and if she is not a WOCBP OR is a WOCBP and is using a contraceptive method that is highly effective (with a failure rate of <1% per year) with low user dependency, or is abstinent from heterosexual intercourse as her preferred and usual lifestyle during the intervention period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/placebo.
• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg at screening and no change in antihypertensive medications within 1 week prior to randomization.
• Has adequate organ function.

Exclusion Criteria:

• Has disease that is suitable for local therapy administered with curative intent (e.g. chemotherapy and radiation for Stage 3 disease).
• Has tumor with any neuroendocrine or small cell component.
• Has a history of a gastrointestinal condition or procedure (e.g. gastric bypass, malabsorption) that, in the opinion of the investigator, may affect oral drug absorption.
• Has had major surgery within 3 weeks prior to the first dose of study treatment
• Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
• Has radiographic evidence of major blood vessel invasion/infiltration, or has had clinically significant hemoptysis (≥0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks prior to the first dose of study treatment.
• Has had significant cardiovascular impairment within 12 months of the first dose of study treatment, such as history of New York Heart Association (NYHA) >Class II congestive heart failure, unstable angina, myocardial infarction or cerebrovascular accident (CVA)/stroke, cardiac revascularization procedure, or cardiac arrhythmia associated with hemodynamic instability.
• Has known intolerance or severe hypersensitivity (Grade ≥3) to pembrolizumab or lenvatinib or any of their excipients
• Has received lenvatinib as monotherapy or in combination with a programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitor or has previously been enrolled in a clinical study evaluating lenvatinib for bladder cancer, regardless of the treatment received.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 inhibitor, indoleamine-pyrrole 2,3 dioxygenase (IDO1) inhibitor, or agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], OX 40, CD137), or any other antibody or drug targeting T-cell costimulatory pathways in the adjuvant or advanced/metastatic setting.
• Has received prior radiotherapy to a metastatic site without the use of chemotherapy radiosensitization within 3 weeks of the first dose of study treatment, with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks before the start of study treatment. Participants must have recovered from all radiation-related toxicities, and must not require corticosteroids.
• Has received a live vaccine within 30 days prior to the first dose of study treatment.
• In the investigator’s judgment, has not recovered from toxicity or other complications from any major surgery prior to starting study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has history or presence of an abnormal electrocardiogram (ECG) that, in the investigator’s opinion, is clinically meaningful.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at a dose exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.
• Has had an active malignancy (except locally advanced or metastatic UC) within the past 36 months. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded.
• Has a history of prostate cancer (T2NXMX or lower with Gleason score ≤7) treated with definitive intent (surgically or with radiation therapy) ≥1 year prior to study entry is acceptable, provided that the participant is considered prostate cancer-free.
• Has central nervous system (CNS) metastases, unless the participant has completed local therapy (e.g. whole brain radiation therapy, surgery, or radiosurgery) and has discontinued use of corticosteroids for this indication for ≥4 weeks before starting study treatment. Any signs (e.g. radiologic) or symptoms of CNS metastases must be stable for ≥4 weeks before starting study treatment.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e, with disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• Has a history of (non-infectious) pneumonitis that required systemic steroids, or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of or is positive for active hepatitis B virus (HBV) or has active hepatitis C virus (HCV).
• Has active tuberculosis (TB).
• Is receiving hemodialysis.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and lenvatinib/placebo.
• Has had an allogeneic tissue/solid organ transplant.

Contact:

• Toll Free Number
• Trialsites@merck.com
• 1-888-577-8839

Locations:

• Banner MD Anderson Cancer Center ( Site 0016)
• Gilbert Arizona 85234 United States

• John Wayne Cancer Institute ( Site 0017)
• Santa Monica California 90404 United States

• University of Chicago ( Site 0039)
• Chicago Illinois 60637 United States

• Joliet Oncology Hematology ( Site 0091)
• Joliet Illinois 60436 United States

• Quincy Medical Group ( Site 0022)
• Quincy Illinois 62301 United States

• New England Cancer Specialists ( Site 0047)
• Scarborough Maine 04074 United States

• Mercy Hospital Saint Louis – David C. Pratt Cancer Center ( Site 0095)
• Saint Louis Missouri 63141 United States

• Comprehensive Cancer Centers of Nevada ( Site 0005)
• Las Vegas Nevada 89169 United States

• Thomas Jefferson University Hospital ( Site 0051)
• Philadelphia Pennsylvania 19107 United States

• Medical University of South Carolina-Hollings Cancer Center ( Site 0029)
• Charleston South Carolina 29425 United States

• Virginia Cancer Institute ( Site 0099)
• Richmond Virginia 23230 United States

• Cancer Care Northwest ( Site 0009)
• Spokane Washington 99218 United States

• Centro de Investigaciones Clinicas – Clinica Viedma ( Site 0585)
• Viedma Rio Negro R8500ACE Argentina

• Centro Oncológico de Rosario ( Site 0584)
• Rosario Santa Fe S2000KZE Argentina

• Instituto de Investigaciones Metabolicas ( Site 0589)
• Buenos Aires C1012AAR Argentina

• CEMAIC ( Site 0581)
• Cordoba X5008HHW Argentina

• Macquarie University ( Site 0151)
• North Ryde New South Wales 2109 Australia

• Austin Health-Austin Hospital ( Site 0154)
• Heidelberg Victoria 3084 Australia

• Juravinski Cancer Centre ( Site 0101)
• Hamilton Ontario L8V 5C2 Canada

• Lakeridge Health ( Site 0103)
• Oshawa Ontario L1G 2B9 Canada

• Sunnybrook Research Institute ( Site 0106)
• Toronto Ontario M4N 3M5 Canada

• CIUSSS de l Estrie Centre Hospitalier Universitaire de Sherbrooke ( Site 0102)
• Sherbrooke Quebec J1H 5N4 Canada

• CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 0104)
• Quebec G1R 2J6 Canada

• Rigshospitalet ( Site 0680)
• Copenhagen 2100 Denmark

• Herlev Hospital ( Site 0681)
• Herlev 2730 Denmark

• Odense Universitetshospital ( Site 0682)
• Odense 5000 Denmark

• Institut de Cancerologie de l Ouest Site Paul Papin ( Site 0236)
• Angers 49055 France

• Centre Hospitalier de la Cote Basque ( Site 0239)
• Bayonne 64109 France

• CHU de Bordeaux- Hopital Saint Andre ( Site 0235)
• Bordeaux 33075 France

• CHD Vendee ( Site 0251)
• La Roche sur Yon 85925 France

• Hopital de la Timone ( Site 0246)
• Marseille 13005 France

• Centre de Cancerologie du Grand Montpellier ( Site 0249)
• Montpellier 34070 France

• Centre D Oncologie de Gentilly ( Site 0240)
• Nancy 54100 France

• Institut Curie ( Site 0237)
• Paris 75005 France

• CHU Poitiers ( Site 0253)
• Poitiers 86021 France

• CHIC Quimper ( Site 0245)
• Quimper 29107 France

• Centre Rene Gauducheau ICO ( Site 0250)
• Saint Herblain 44805 France

• Hopital Civil-CHU de Strasbourg ( Site 0232)
• Strasbourg 67091 France

• Institut Gustave Roussy ( Site 0243)
• Villejuif 94805 France

• Universitaetsmedizin Goettingen ( Site 0281)
• Gottingen 37075 Germany

• Universitaetsklinikum Hamburg-Eppendorf ( Site 0282)
• Hamburg 20246 Germany

• Klinikum der Eberhard-Karls-Universitaet Tuebingen ( Site 0271)
• Tuebingen 72076 Germany

• Bajcsy Zsilinszki Korhaz es Rendelointezet ( Site 0509)
• Budapest 1106 Hungary

• Orszagos Onkologiai Intezet ( Site 0503)
• Budapest 1122 Hungary

• Uzsoki Utcai Korhaz ( Site 0508)
• Budapest 1145 Hungary

• Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 0504)
• Kaposvar 7400 Hungary

• Bacs-Kiskun Megyei Korhaz ( Site 0510)
• Kecskemet 6000 Hungary

• Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz ( Site 0506)
• Miskolc 3526 Hungary

• Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 0507)
• Szolnok 5000 Hungary

• Rambam Medical Center ( Site 0552)
• Haifa 3109601 Israel

• Shaare Zedek Medical Center ( Site 0559)
• Jerusalem 9103102 Israel

• Hadassah Ein Kerem Medical Center ( Site 0558)
• Jerusalem 9112001 Israel

• Meir Medical Center ( Site 0554)
• Kfar Saba 4428164 Israel

• Rabin Medical Center ( Site 0553)
• Petach-Tikwa 4941492 Israel

• Sheba Medical Center ( Site 0551)
• Ramat Gan 5265601 Israel

• Assaf Harofeh Medical Center ( Site 0556)
• Zerifin 7030001 Israel

• Centro di Riferimento Oncologico CRO ( Site 0304)
• Aviano PN 33081 Italy

• Istituto Tumori Giovanni Paolo II ( Site 0306)
• Bari 70124 Italy

• Policlinico S. Orsola – Malpighi (Bologna) ( Site 0302)
• Bologna 40138 Italy

• Azienda Ospedaliera per l Emergenza Cannizzaro ( Site 0305)
• Catania 95126 Italy

• ASST Grande Ospedale Metropolitano Niguarda ( Site 0307)
• Milano 20162 Italy

• Azienda Ospedaliera Santa Maria ( Site 0303)
• Terni 05100 Italy

• Hirosaki University Hospital ( Site 0123)
• Hirosaki Aomori 036-8563 Japan

• National Cancer Center Hospital East ( Site 0128)
• Kashiwa Chiba 277-8577 Japan

• Ehime University Hospital ( Site 0137)
• Toon Ehime 791-0295 Japan

• Sapporo Medical University Hospital ( Site 0122)
• Sapporo Hokkaido 060-8543 Japan

• University of Tsukuba Hospital ( Site 0126)
• Tsukuba Ibaraki 305-8576 Japan

• Kitasato University Hospital ( Site 0129)
• Sagamihara Kanagawa 252-0375 Japan

• Nara Medical University Hospital ( Site 0133)
• Kashihara Nara 634-8522 Japan

• Saitama Medical University International Medical Center ( Site 0125)
• Hidaka Saitama 350-1298 Japan

• Yamaguchi University Hospital ( Site 0135)
• Ube Yamaguchi 755-8505 Japan

• Akita University Hospital ( Site 0124)
• Akita 010-8543 Japan

• Chiba Cancer Center ( Site 0127)
• Chiba 260-8717 Japan

• Nagasaki University Hospital ( Site 0136)
• Nagasaki 852-8501 Japan

• Osaka City University Hospital ( Site 0132)
• Osaka 545-8586 Japan

• Tokushima University Hospital ( Site 0134)
• Tokushima 770-8503 Japan

• Medical Hospital, Tokyo Medical And Dental University ( Site 0130)
• Tokyo 113-8519 Japan

• Chungnam National University Hospital ( Site 0195)
• Daejeon Chungnam 35015 Korea, Republic of

• National Cancer Center ( Site 0196)
• Goyang-si 10408 Korea, Republic of

• Chonnam National University Hwasun Hospital ( Site 0194)
• Hwasun Gun 58128 Korea, Republic of

• Korea University Anam Hospital ( Site 0197)
• Seoul 02841 Korea, Republic of

• Seoul National University Hospital ( Site 0191)
• Seoul 03080 Korea, Republic of

• Severance Hospital ( Site 0192)
• Seoul 03722 Korea, Republic of

• Veterans Health Service Medical Center ( Site 0198)
• Seoul 05368 Korea, Republic of

• Samsung Medical Center ( Site 0193)
• Seoul 06351 Korea, Republic of

• Amphia Ziekenhuis Breda ( Site 0331)
• Breda 4819 EV Netherlands

• Haga Ziekenhuis ( Site 0333)
• Den Haag 2545 AA Netherlands

• Maastricht Universitair Medisch Centrum – MUMC ( Site 0334)
• Maastricht 6229 HX Netherlands

• Erasmus MC ( Site 0332)
• Rotterdam 3015 GD Netherlands

• St. Antonius Ziekenhuis ( Site 0335)
• Utrecht 3543 EM Netherlands

• Szpital Miejski im. Jana Pawła II w Bielsku-Białej ( Site 0542)
• Bielsko-Biala 43-300 Poland

• Europejskie Centrum Zdrowia Otwock ( Site 0532)
• Otwock 05-400 Poland

• Urologica Praktyka Lekarska Adam Marcheluk ( Site 0543)
• Siedlce 08-110 Poland

• Szpital Wojewodzki ( Site 1062)
• Tarnow 33-100 Poland

• Magodent Szpital Elblaska ( Site 0541)
• Warszawa 01-748 Poland

• Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 0535)
• Wroclaw 50-556 Poland

• Russian Scientific Center of Roentgenoradiology ( Site 0424)
• Moscow 117997 Russian Federation

• Central Clinical Hospital with Polyclinic ( Site 0415)
• Moscow 121359 Russian Federation

• Medical Rehabilitation Center ( Site 0411)
• Moscow 125367 Russian Federation

• Murmansk Regional Oncology Dispensary ( Site 0420)
• Murmansk 183057 Russian Federation

• Volga District Medical Center Federal Medical and Biological Agency ( Site 0413)
• Nizhny Novgorod 603074 Russian Federation

• Omsk Clinical Oncology Dispensary ( Site 0418)
• Omsk 644013 Russian Federation

• Clinical Hospital Saint Luka ( Site 0421)
• Saint-Petersburg 194044 Russian Federation

• Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0414)
• Yaroslavl 150054 Russian Federation

• Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0351)
• Badalona Barcelona 08916 Spain

• Hospital Teresa Herrera – Chuac ( Site 0357)
• A Coruna 15006 Spain

• Hospital Infanta Cristina ( Site 0355)
• Badajoz 06080 Spain

• Hospital General Universitari Vall d Hebron ( Site 0358)
• Barcelona 08035 Spain

• Hospital Universitario Gregorio Maranon ( Site 0352)
• Madrid 28009 Spain

• Hospital Universitario HM Sanchinarro ( Site 0356)
• Madrid 28050 Spain

• Xarxa Assistencial Universitaria Manresa ( Site 0354)
• Manresa 08243 Spain

• Kaohsiung Chang Gung Memorial Hospital ( Site 0217)
• Kaohsiung 833 Taiwan

• Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0216)
• Kaoshiung 807 Taiwan

• China Medical University Hospital ( Site 0213)
• Taichung 40447 Taiwan

• Taichung Veterans General Hospital ( Site 0214)
• Taichung 407 Taiwan

• National Cheng Kung University Hospital ( Site 0215)
• Tainan 70403 Taiwan

• National Taiwan University Hospital ( Site 0211)
• Taipei 10048 Taiwan

• Taipei Veterans General Hospital ( Site 0212)
• Taipei 11217 Taiwan

• Cukurova Universitesi Tıp Fakultesi Balcalı Hastanesi ( Site 0457)
• Adana 01330 Turkey

• Ankara Sehir Hastanesi ( Site 0455)
• Ankara 06800 Turkey

• Antalya Memorial Hospital Department of Medical Oncology ( Site 0461)
• Antalya 07020 Turkey

• Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0454)
• Istanbul 34098 Turkey

• Medeniyet Uni. Goztepe Egitim ve Arast. Hast. ( Site 0459)
• Istanbul 34722 Turkey

• Ege Universitesi Tulay Aktas Onkoloji Hastanesi ( Site 0462)
• İzmir 35100 Turkey

• Necmettin Erbakan Universitesi Meram Tip Fakultesi Hastanesi ( Site 0456)
• Konya 42080 Turkey

• Sakarya Universitesi Tip Fakultesi Arastirma Hastanesi ( Site 0460)
• Sakarya 54290 Turkey

• Queens Hospital-Purple Zone ( Site 0377)
• Romford Essex RM7 0AG United Kingdom

• Lister Hospital ( Site 0376)
• Stevenage Herts SG1 4AB United Kingdom

• Kent and Canterbury Hospital ( Site 0390)
• Canterbury Kent CT1 3NG United Kingdom

• Nottingham University Hospital NHS Trust ( Site 0383)
• Nottingham Nottinghamshire NG5 1PB United Kingdom

• Saint Bartholomew s Hospital – London ( Site 0386)
• London EC1A 7BE United Kingdom

• University College London Hospital NHS Foundation Trust ( Site 0380)
• London NW1 2PG United Kingdom

• Derriford Hospital ( Site 0388)
• Plymouth PL6 8DH United Kingdom

• Royal Preston Hospital ( Site 0379)
• Preston PR2 9HT United Kingdom

• Weston Park Hospital ( Site 0387)
• Sheffield S10 2SJ United Kingdom

View trial on ClinicalTrials.gov