Long-term Safety and Efficacy Extension Study for Participants With Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab (MK-3475) Study (MK-3475-587/KEYNOTE-587)

Solid Tumors Clinical Trial

Official title:

A Multicenter, Open-label, Phase 3 Study to Evaluate the Long-term Safety and Efficacy in Participants Who Are Currently on Treatment or in Follow-up in Studies That Include Pembrolizumab

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03486873
• Other study ID #: 3475-587
• Secondary ID: MK-3475-587KEYNO
• Status: Recruiting
• Phase: Phase 3
• Start date: August 21, 2018
• Est. completion date: August 4, 2043

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the long-term safety and efficacy of pembrolizumab (MK-3475) in participants from previous Merck pembrolizumab-based parent studies who transition into this extension study.

This study will consist of three phases: 1) First Course Phase, 2) Survival Follow-up Phase or 3) Second Course Phase. Each participant will transition to this extension study in one of the following three phases, depending on the study phase they were in at the completion of the parent study. Participants who were in the First Course Phase of study treatment with pembrolizumab or lenvatinib in their parent study will enter the First Course Phase of this study and complete up to 35 doses or more every 3 weeks (Q3W) or 17 doses or more every 6 weeks (Q6W) of study treatment with pembrolizumab or a pembrolizumab-based combination or lenvatinib according to arm assignment. Participants who were in the Follow-up Phase in the parent study (post-treatment or Survival Follow-up Phase) will enter the Survival Follow-up Phase of this study. Participants who were in the Second Course Phase in their parent study will enter Second Course Phase of this study and complete up to 17 doses Q3W or 8 doses Q6W of study treatment with pembrolizumab or a pembrolizumab-based combination according to arm assignment.

Any participant originating from a parent trial where crossover to pembrolizumab was permitted upon disease progression may be eligible for 35 doses as Q3W or 17 doses Q6W of pembrolizumab (approximately 2 years), if they progress while on the control arm and pembrolizumab is approved for the indication in the country where the potential eligible crossover participant is being evaluated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3500
• Est. completion date: August 4, 2043
• Est. primary completion date: August 4, 2043
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Treated on the parent pembrolizumab studies established by the Sponsor as MK-3475-587 ready.

• Currently receiving pembrolizumab, pembrolizumab based combinations or lenvatinib from parent studies or in a follow-up phase.

Additional eligibility criteria for participants who enter Second Course Phase once they are enrolled on MK-3475-587:

• Has not received any anticancer systemic treatment since the last dose of pembrolizumab or a pembrolizumab-based combination in First Course Phase.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Demonstrates adequate organ function.

• Have resolution of any toxic effect(s) of First Course Phase trial treatment with pembrolizumab or a pembrolizumab-based combination to Grade 1 or less (except alopecia) before trial treatment in Second Course Phase is started. If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications of the intervention.

• A female participant is eligible to enroll if she is not pregnant, not breastfeeding, and =1 of the following conditions applies: A woman of childbearing potential (WOCBP) who agrees to use contraception during the study treatment period and for =120 days (corresponding to time needed to eliminate any study combination treatment(s) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity.

Additional eligibility criteria for participants who enter dosing with Lenvatinib:

• Adequately controlled blood pressure (BP) to <150/90 mmHg, with or without antihypertensive medications.

• For male agrees to be abstinent from penile-vaginal intercourse OR agrees to use a highly effective contraceptive method while receiving study drug and for 7 days after the last dose of lenvatinib.

• Is female and not pregnant/breastfeeding and at least one of the following applies during the study and for =4 days after: is not a woman of childbearing potential (WOCBP), is a WOCBP and uses highly effective contraception (low user dependency method OR a user dependent hormonal method in combination with a barrier method) or is a WOCBP who is abstinent from heterosexual intercourse.

Exclusion Criteria:

-There are no exclusion criteria to participate in MK-3475-587.

Participants are excluded from entering Second Course trial treatment once they are enrolled on MK-3475-587 if any of the following criteria applies:

• Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients.

• Has received a live vaccine within 30 days prior to the first dose of Second Course Phase trial treatment.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the Cycle 1 Day 1 of Second Course Phase.

• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early stage cancers (carcinoma in situ or Stage 1) treated with curative intent, melanoma (non-ulcerated, thin primary), basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.

• Has known active central nervous system metastases and/or carcinomatous meningitis.

• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.

• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Note: Participants that experienced pneumonitis during First Course that did not meet the criteria for permanent discontinuation are eligible.

• Non-small cell lung cancer (NSCLC) participants only: Has interstitial lung disease.

• 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 hepatitis B or hepatitis C. For parent studies where inclusion of participants with hepatitis was permitted, MK-3475-587 will follow the parent study eligibility criteria for hepatitis.

• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Second Course Phase eligibility Visit through 120 days after the last dose of study treatment.

• Has severe cardiovascular disease, i.e., arrhythmias, requiring chronic treatment, congestive heart failure (New York Heart Association Class III or IV) or symptomatic ischemic heart disease.

• Has hepatic decompensation (Child-Pugh score >6 [class B and C]).

• Has uncontrolled thyroid dysfunction.

• Has uncontrolled diabetes mellitus.

• Has had an allogeneic tissue/solid organ transplant.

• Has a known history of active tuberculosis (TB; Bacillus tuberculosis).

Additional exclusion criteria for participants who enter dosing with Lenvatinib:

• Has had major surgery within 3 weeks prior to first dose of study intervention(s).

• Has preexisting =Grade 3 gastrointestinal or non-gastrointestinal fistula.

• Has urine protein =1 g/24 hours.

• Has LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).

• Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation.

• Prolongation of QT intervals corrected for heart rate using Fridericia's (cube root) correction (QTcF) interval to >480 ms.

• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.

• Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.

• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.

• Has a history of any contraindication or has a severe hypersensitivity to any components of lenvatinib.

Related Conditions & MeSH terms

• Hematologic Malignancies
• Hematologic Neoplasms
• Solid Tumors

Intervention

Drug:
• Pembrolizumab
200 or 400 mg IV infusion
• Standard of Care (SOC)
IV infusion or oral tablets
• Lenvatinib
Oral capsules

Locations

Country	Name	City	State
Argentina	Centro de Oncología e Investigación de Buenos Aires ( Site 1357)	Berazategui	Buenos Aires
Argentina	Hospital Aleman-Oncology ( Site 1351)	Buenos Aires	Caba
Argentina	IDIM - Instituto de Investigaciones Metabólicas ( Site 1362)	Ciudad de Buenos Aires	Buenos Aires
Argentina	Hospital Privado Universitario de Córdoba ( Site 1354)	Cordoba
Argentina	Fundación CORI para la Investigación y Prevención del Cáncer ( Site 1358)	La Rioja
Argentina	Instituto de Oncologia de Rosario ( Site 1350)	Rosario	Santa Fe
Argentina	Sanatorio Parque ( Site 1355)	Rosario	Santa Fe
Argentina	Centro Medico San Roque-Oncology ( Site 1352)	Tucuman
Argentina	Clinica Viedma ( Site 1353)	Viedma	Rio Negro
Australia	Royal Adelaide Hospital ( Site 3014)	Adelaide	South Australia
Australia	Gallipoli Medical Research Ltd ( Site 3011)	Brisbane	Queensland
Australia	Mater Misericordiae Limited-Medical Oncology ( Site 3019)	Brisbane	Queensland
Australia	Chris OBrien Lifehouse ( Site 3003)	Camperdown	New South Wales
Australia	Royal Prince Alfred Hospital-A.W. Morrow Gastroenterology and Liver Centre ( Site 3016)	Camperdown	New South Wales
Australia	Monash Health ( Site 3015)	Clayton	Victoria
Australia	Austin Health-Austin Hospital ( Site 3004)	Heidelberg	Victoria
Australia	Royal Brisbane and Women s Hospital ( Site 3009)	Herston	Queensland
Australia	Liverpool Hospital-Medical Oncology ( Site 3021)	Liverpool	New South Wales
Australia	Macquarie University ( Site 3010)	Macquarie University	New South Wales
Australia	Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 3008)	Melbourne	Victoria
Australia	St Vincent's Hospital-Oncology Clinical Trials ( Site 3018)	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital ( Site 3006)	Nedlands	Western Australia
Australia	Mater Hospital Sydney ( Site 3007)	North Sydney	New South Wales
Australia	Orange Hospital-Clinical Trials Unit ( Site 3027)	Orange	New South Wales
Australia	Port Macquarie - Mid North Coast Cancer Institute-Medical Oncology ( Site 3020)	Port Macquarie	New South Wales
Australia	Tasman Oncology Research Pty Ltd ( Site 3012)	Southport	Queensland
Australia	Western Health-Sunshine & Footscray Hospitals ( Site 3023)	St Albans	Victoria
Australia	Royal North Shore Hospital-Medical Oncology Clinical Trials ( Site 3025)	St Leonards	New South Wales
Australia	St John of God Subiaco Hospital ( Site 3013)	Subiaco	Western Australia
Australia	The Townsville Hospital ( Site 3017)	Townsville	Queensland
Australia	Calvary Mater Newcastle ( Site 3005)	Waratah	New South Wales
Australia	Ballarat Oncology & Haematology Services ( Site 3022)	Wendouree	Victoria
Australia	Westmead Hospital ( Site 3000)	Westmead	New South Wales
Australia	Melanoma Institute Australia ( Site 3001)	Wollstonecraft	New South Wales
Australia	The Queen Elizabeth Hospital ( Site 3026)	Woodville	South Australia
Australia	Princess Alexandra Hospital ( Site 3002)	Woolloongabba	Queensland
Austria	Medical University of Graz ( Site 2952)	Graz	Steiermark
Austria	Medizinische Universitaet Innsbruck ( Site 2951)	Innsbruck	Tirol
Austria	Kepler Universitätsklinikum ( Site 2955)	Linz	Oberosterreich
Austria	Uniklinikum Salzburg ( Site 2956)	Salzburg
Austria	Klinik Floridsdorf-Abteilung für Innere Medizin und Pneumologie ( Site 2954)	Wien
Austria	Medizinische Universität Wien ( Site 2953)	Wien
Belgium	Institut Jules Bordet ( Site 2903)	Anderlecht	Bruxelles-Capitale, Region De
Belgium	UZ Brussel ( Site 2900)	Brussels	Bruxelles-Capitale, Region De
Belgium	Cliniques Universitaires de Bruxelles - CUB - Hopital Erasme ( Site 2905)	Bruxelles	Bruxelles-Capitale, Region De
Belgium	AZ Maria Middelares ( Site 2908)	Gent	Oost-Vlaanderen
Belgium	UZ Leuven ( Site 2901)	Leuven	Vlaams-Brabant
Belgium	UZ Leuven - Campus Gasthuisberg ( Site 2906)	Leuven	Vlaams-Brabant
Belgium	UZ Leuven Gasthuisberg, Gynaecologie-Verloskunde ( Site 2907)	Leuven	Vlaams-Brabant
Belgium	AZ Sint-Maarten ( Site 2904)	Mechelen	Antwerpen
Belgium	Université Catholique de Louvain-Namur - Centre Hospitalier Universitaire Dinant-Godinne - Site Godi	Yvoir	Namur
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos ( Site 1010)	Barretos	Sao Paulo
Brazil	CEPON ( Site 1012)	Florianópolis	Santa Catarina
Brazil	CRIO - CENTRO REGIONAL INTEGRADO DE ONCOLOGIA-Pesquisa Clínica ( Site 1024)	Fortaleza	Ceara
Brazil	ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 1008)	Ijui	Rio Grande Do Sul
Brazil	Hospital de Clinicas de Porto Alegre ( Site 1000)	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conceição ( Site 1011)	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital São Lucas da PUCRS-Centro de Pesquisa em Oncologia ( Site 1006)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto de de Educação, pesquisa e Gestão em Saúde ( Site 1014)	Rio de Janeiro
Brazil	Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA ( Site 1020)	Rio de Janeiro
Brazil	Clinica Viver ( Site 1021)	Santa Maria	Rio Grande Do Sul
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto-Centro Integrado de Pesquisa ( Site	São José do Rio Preto	Sao Paulo
Brazil	A. C. Camargo Cancer Center ( Site 1002)	Sao Paulo
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 1001)	Sao Paulo
Brazil	Clínica de Pesquisa e Centro de Estudos em Ginecologia Oncológica e Mamária LTDA ( Site 1017)	São Paulo	Sao Paulo
Canada	Cross Cancer Institute ( Site 2804)	Edmonton	Alberta
Canada	Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre-Oncology ( Site 2809)	Greenfield Park	Quebec
Canada	Hamilton Health Sciences-Juravinski Cancer Centre ( Site 2801)	Hamilton	Ontario
Canada	Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 2808)	Kingston	Ontario
Canada	Centre Intégré de Santé et de Services Sociaux (CISSS) de La-Centre intégré de cancérologie de Lava	Laval	Quebec
Canada	London Regional Cancer Program - LHSC ( Site 2806)	London	Ontario
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 2807)	Montreal	Quebec
Canada	Jewish General Hospital ( Site 2800)	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus ( Site 2813)	Ottawa	Ontario
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 2	Quebec
Canada	Mount Sinai Hospital ( Site 2811)	Toronto	Ontario
Canada	Princess Margaret Cancer Centre ( Site 2803)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 2802)	Toronto	Ontario
Chile	Bradfordhill-Clinical Area ( Site 2756)	Santiago	Region M. De Santiago
Chile	Fundacion Arturo Lopez Perez FALP ( Site 2750)	Santiago	Region M. De Santiago
Chile	Instituto Nacional del Cancer-CR Investigación ( Site 2753)	Santiago	Region M. De Santiago
Chile	Orlandi Oncologia-Oncology ( Site 2752)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile-Hemato-Oncology ( Site 2751)	Santiago	Region M. De Santiago
Chile	James Lind Centro de Investigación del Cáncer ( Site 2757)	Temuco	Araucania
Chile	Centro de Investigaciones ( Site 2755)	Viña del Mar	Valparaiso
Chile	ONCOCENTRO APYS-ACEREY ( Site 2758)	Viña del Mar	Valparaiso
China	Affiliated Hospital of Military Medical Science Academy of the PLA ( Site 3465)	Beijing	Beijing
China	Beijing Cancer Hospital ( Site 3451)	Beijing	Beijing
China	Beijing Cancer hospital-Thoracic Cancer Department A ( Site 3454)	Beijing	Beijing
China	Beijing Peking Union Medical College Hospital-Medical Oncology ( Site 3466)	Beijing	Beijing
China	Jilin Province Tumor Hospital ( Site 3484)	Changchun	Jilin
China	The First Hospital of Jilin University-Oncology ( Site 3464)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 3485)	Changsha	Hunan
China	Xiangya Hospital Central South University-Respiratory ( Site 3479)	Changsha	Hunan
China	West China Hospital Sichuan University-respiratory ( Site 3473)	Cheng Du	Sichuan
China	Army Medical Center of People's Liberation Army-Oncology Department ( Site 3477)	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital ( Site 3461)	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital-Cancer Center ( Site 3462)	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center-melanoma ( Site 3482)	Guangzhou	Guangdong
China	SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal Medicine ( Site 3452)	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University-thoracic surgery department ( Site 346	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University-pneumology department ( Site 3459)	Guangzhou	Guangdong
China	Hangzhou Cancer Hospital-Medical Oncology ( Site 3468)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 3481)	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital-Harbin Medical University Cancer Hospital ( Site 3475)	Harbin	Heilongjiang
China	Anhui Provincial Hospital-Cancer Chemotherapy Department ( Site 3480)	Hefei	Anhui
China	Anhui Provincil Hospital South District-Respiratory Medicine Dept ( Site 3487)	Hefei	Anhui
China	Jiangsu Cancer Hospital-Medical Oncotherapy ( Site 3469)	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center ( Site 3467)	Shanghai	Shanghai
China	Shanghai Pulmonary Hospital ( Site 3470)	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute and Hospital ( Site 3456)	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical,Science & Technology-oncology ( Site 3476)	Wuhan	Hubei
China	Tangdu Hospital of Fourth Military Medical University of Chi-department of radiotherapy ( Site 3455)	Xi'an	Shaanxi
China	Northern Jiangsu People's Hospital-General Surgery Department ( Site 3474)	Yangzhou	Jiangsu
Colombia	Administradora Country S.A. ( Site 2701)	Bogota	Distrito Capital De Bogota
Colombia	Fundación Valle del Lili ( Site 2700)	Cali	Valle Del Cauca
Colombia	Instituto de Cancerología-Oncology ( Site 2702)	Medellín	Antioquia
Colombia	Oncomédica S.A.S ( Site 2703)	Montería	Cordoba
Czechia	Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 0703)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Olomouc ( Site 0701)	Olomouc
Czechia	Fakultni nemocnice Olomouc-Onkologicka klinika ( Site 0704)	Olomouc	Olomoucky Kraj
Czechia	Fakultni Thomayerova nemocnice-Onkologicka klinika 1. LF UK ( Site 0702)	Prague	Praha 4
Czechia	Fakultni nemocnice v Motole-Onkologicka klinika 2. LF UK a FN Motol ( Site 0705)	Praha	Praha 5
Czechia	Fakultni nemocnice v Motole ( Site 0700)	Praha 5
Denmark	Odense Universitetshospital ( Site 0650)	Odense	Syddanmark
Denmark	Vejle Sygehus ( Site 0653)	Vejle	Syddanmark
Estonia	Tartu University Hospital-Radiotherapy and oncology ( Site 3800)	Tartu	Tartumaa
Finland	Tampere University Hospital [Tampere Finland] ( Site 0600)	Tampere	Pirkanmaa
Finland	Turku University Hospital ( Site 0601)	Turku	Varsinais-Suomi
France	CHU Jean Minjoz ( Site 2520)	Besancon	Doubs
France	Hôpital Avicenne-Dermatologie ( Site 2538)	Bobigny	Seine-Saint-Denis
France	Institut Bergonie ( Site 2502)	Bordeaux	Gironde
France	Ambroise Pare Hopital ( Site 2503)	Boulogne	Hauts-de-Seine
France	CHU de Brest -Site Hopital Morvan ( Site 2504)	Brest	Finistere
France	Hopital Trousseau ( Site 2512)	Chambray-les-Tours	Indre-et-Loire
France	Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne-ONCOLOGY ( Site 2542)	Clermont-Ferrand	Puy-de-Dome
France	Hôpital Beaujon ( Site 2524)	Clichy	Ile-de-France
France	Centre Hopitalier Intercommunal Creteil ( Site 2514)	Creteil	Val-de-Marne
France	Centre Georges François Leclerc-Centre de recherche clinique ( Site 2536)	Dijon	Cote-d Or
France	Centre Hospitalier du Mans-Pneumologie ( Site 2527)	Le Mans	Sarthe
France	CHRU Lille Hospital Claude Huriez ( Site 2506)	Lille	Nord
France	Centre Hopitalar Leon-Berard ( Site 2519)	Lyon	Auvergne
France	CHU La Timone ( Site 2508)	Marseille	Bouches-du-Rhone
France	Hopital Nord ( Site 2516)	Marseille	Bouches-du-Rhone
France	Centre Hospitalier Universitaire de Nice - Hôpital l'Archet-Dermatology Department ( Site 2539)	Nice	Alpes-Maritimes
France	CHU Hopital Saint Antoine ( Site 2517)	Paris
France	Groupe hospitalier Paris saint Joseph-Service de Pneumologie-Allergologie -Oncologie Thoracique ( Si	Paris	Ile-de-France
France	Hopital Cochin ( Site 2509)	Paris
France	Hopital Saint Louis ( Site 2510)	Paris
France	Hôpital Tenon ( Site 2530)	Paris
France	CHU Bordeaux Haut-Leveque ( Site 2534)	Pessac	Aquitaine
France	C.H.U. Pontchaillou ( Site 2511)	Pierre Benite	Rhone
France	CH Lyon Sud Hospices Civils de Lyon ( Site 2521)	Pierre Benite	Rhone-Alpes
France	Centre Eugène Marquis Rennes - Centre de Lutte Contre le Cancer ( Site 2525)	Rennes	Ille-et-Vilaine
France	Institut de Cancérologie de l'Ouest-Oncologie Médicale ( Site 2522)	Saint Herblain	Loire-Atlantique
France	Nouvel Hôpital Civil (NHC) ( Site 2529)	Strasbourg	Alsace
France	CHU de Toulouse - Hopital Larrey-service de pneumologie ( Site 2526)	Toulouse	Haute-Garonne
France	CHU Toulouse - Hopital Rangueil ( Site 2518)	Toulouse	Haute-Garonne
France	C.H.U. de Tours - Hopital Bretonneau ( Site 2515)	Tours	Indre-et-Loire
France	Institut de Cancérologie de Lorraine Alexis Vautrin ( Site 2532)	Vandoeuvre-lès-Nancy	Lorraine
France	Hôpital Universitaire Paul Brousse ( Site 2541)	Villejuif	Val-de-Marne
France	Institut Gustave Roussy ( Site 2513)	Villejuif	Val-de-Marne
Germany	Helios Klinikum Emil von Behring Berlin-Zehlendorf-Lungenklinik Heckeshorn ( Site 2418)	Berlin
Germany	Elbe Klinikum Buxtehude ( Site 2400)	Buxtehude	Niedersachsen
Germany	Universitatsklinikum Carl Gustav Carus ( Site 2407)	Dresden	Sachsen
Germany	Universitätsklinikum Erlangen ( Site 2408)	Erlangen	Bayern
Germany	Universitaetsklinikum Essen ( Site 2404)	Essen	Nordrhein-Westfalen
Germany	Krankenhaus Nordwest ( Site 2409)	Frankfurt	Hessen
Germany	SRH Wald-Klinikum Gera GmbH ( Site 2403)	Gera	Thuringen
Germany	LungenClinic Grosshansdorf GmbH ( Site 2412)	Grosshansdorf	Schleswig-Holstein
Germany	Facharztzentrum Eppendorf ( Site 2415)	Hamburg
Germany	Medizinische Hochschule Hannover ( Site 2402)	Hannover	Niedersachsen
Germany	Universitaetsklinikum des Saarlandes-Klinik für Innere Medizin V-Pneumologie, Allergologie, Beatmun	Homburg	Saarland
Germany	Universitaetsklinik Muenchen ( Site 2406)	Muenchen	Bayern
Germany	Universitaetsklinikum Tuebingen ( Site 2405)	Tuebingen	Baden-Wurttemberg
Greece	General Hospital of Athens "Laiko"-Hematology Department ( Site 1851)	Athens	Attiki
Greece	Sotiria Regional Chest Diseases Hospital of Athens ( Site 1850)	Athens	Attiki
Guatemala	Grupo Medico Angeles ( Site 3402)	Guatemala
Guatemala	MEDI-K CAYALA ( Site 3403)	Guatemala
Guatemala	Oncomedica ( Site 3401)	Guatemala
Hong Kong	Queen Mary Hospital ( Site 1902)	Hksar
Hong Kong	Queen Mary Hospital-Department of Medicine (Respiratory) ( Site 1900)	Hksar
Hungary	Orszagos Koranyi Pulmonologiai Intezet ( Site 1403)	Budapest
Hungary	Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 1411)	Budapest	Pest
Hungary	Semmelweis University-Belgyógyászati és Hematológiai Klinika ( Site 1406)	Budapest
Hungary	Uzsoki Utcai Kórház-Onkoradiológiai Osztály ( Site 1413)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont-Belgyógyászati Klinika (Haematologia) ( Site 1415)	Debrecen
Hungary	Debreceni Egyetem Klinikai Kozpont-Onkológiai Klinika ( Site 1412)	Debrecen
Hungary	Farkasgyepui Tudogyogyintezet-Pulmonologia ( Site 1414)	Farkasgyepu	Veszprem
Hungary	Békés Megyei Központi Kórház Pándy Kálmán Tagkórház-Megyei Onkológiai Centrum ( Site 1405)	Gyula	Bekes
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 1402)	Kaposvar
Hungary	Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház ( Site 1409)	Miskolc	Borsod-Abauj-Zemplen
Hungary	Fejér Megyei Szent György Egyetemi Oktató Kórház-l.Pulmonologia ( Site 1407)	Székesfehérvár	Fejer
Hungary	Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 1401)	Szolnok	Jasz-Nagykun-Szolnok
Hungary	Markusovszky Egyetemi Oktatokorhaz-Onkológiai Osztály ( Site 1410)	Szombathely	Vas
Hungary	Zala Megyei Szent Rafael Korhaz ( Site 1400)	Zalaegerszeg
Ireland	Mater Misercordiae University Hospital ( Site 1800)	Dublin	Leinster
Ireland	St. James s Hospital ( Site 1801)	Dublin
Ireland	Tallaght University Hospital ( Site 1803)	Dublin
Israel	Rambam Health Care Campus-Oncology Division ( Site 2053)	Haifa
Israel	Hadassah Ein Kerem Medical Center ( Site 2051)	Jerusalem
Israel	Rabin Medical Center ( Site 2059)	Petah-Tikva
Israel	Chaim Sheba Medical Center ( Site 2055)	Ramat Gan
Israel	Chaim Sheba Medical Center. ( Site 2052)	Ramat Gan
Israel	Sourasky Medical Center ( Site 2054)	Tel Aviv
Israel	Shamir Medical Center Assaf Harofeh ( Site 2058)	Zerifin
Italy	IRCCS CRO Aviano, Hematology/Oncology ( Site 1957)	Aviano	Pordenone
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII-UOC Oncologia ( Site 1967)	Bergamo
Italy	Humanitas Gavazzeni ( Site 1954)	Bergamo
Italy	Azienda Ospedaliera Spedali Civili di Brescia-Oncology ( Site 1972)	Brescia
Italy	Istituto di Candiolo - IRCCS ( Site 1960)	Candiolo	Torino
Italy	IRCCS A.O.U. San Martino - IST ( Site 1961)	Genova
Italy	Istituto Europeo di Oncologia ( Site 1952)	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1955)	Napoli
Italy	Ospedale San Luigi Gonzaga ( Site 1956)	Orbassano	Piemonte
Italy	Azienda Ospedaliero Universitaria di Parma-UO Oncologia Medica ( Site 1964)	Parma
Italy	AO Santa Maria della Misericordia-Oncology Department ( Site 1971)	Perugia	Umbria
Italy	Azienda Ospedaliera San Camillo Forlanini ( Site 1958)	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS -Medical Oncology ( Site 1975)	Roma	Lazio
Italy	Policlinico Universitario Agostino Gemelli ( Site 1965)	Roma	Lazio
Italy	Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1968)	Rozzano	Milano
Italy	ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 1969)	Siena
Italy	Azienda Ospedaliera Santa Maria ( Site 1962)	Terni
Japan	Hyogo Cancer Center ( Site 3131)	Akashi	Hyogo
Japan	Tokyo Medical and Dental University Hospital ( Site 3149)	Bunkyo	Tokyo
Japan	Chiba Cancer Center ( Site 3117)	Chiba
Japan	Kyushu University Hospital ( Site 3143)	Fukuoka
Japan	National Hospital Organization Kyushu Cancer Center ( Site 3169)	Fukuoka
Japan	National Hospital Organization Kyushu Medical Center ( Site 3136)	Fukuoka
Japan	Gifu University Hospital ( Site 3161)	Gifu
Japan	Osaka Habikino Medical Center ( Site 3138)	Habikino	Osaka
Japan	Saitama Medical University International Medical Center ( Site 3118)	Hidaka	Saitama
Japan	National Hospital Organization Himeji Medical Center ( Site 3111)	Himeji	Hyogo
Japan	Kansai Medical University Hospital ( Site 3126)	Hirakata	Osaka
Japan	Hiroshima City Hiroshima Citizens Hospital ( Site 3119)	Hiroshima
Japan	Hiroshima University Hospital ( Site 3154)	Hiroshima
Japan	Kanazawa University Hospital ( Site 3140)	Kanazawa	Ishikawa
Japan	Nara Medical University Hospital ( Site 3110)	Kashihara	Nara
Japan	National Cancer Center Hospital East ( Site 3121)	Kashiwa	Chiba
Japan	Kagawa University Hospital ( Site 3171)	Kita	Kagawa
Japan	Saitama Cancer Center ( Site 3112)	Kitaadachi-gun	Saitama
Japan	Kobe City Medical Center General Hospital ( Site 3144)	Kobe	Hyogo
Japan	Kochi Health Sciences Center ( Site 3145)	Kochi
Japan	Dokkyo Medical University - Koshigaya Hospital ( Site 3152)	Koshigaya	Saitama
Japan	Japanese Foundation for Cancer Research ( Site 3146)	Koto	Tokyo
Japan	Japanese Foundation for Cancer Research ( Site 3164)	Koto	Tokyo
Japan	Kurashiki Central Hospital ( Site 3132)	Kurashiki	Okayama
Japan	Kurume University Hospital ( Site 3105)	Kurume	Fukuoka
Japan	National Hospital Organization Shikoku Cancer Center ( Site 3116)	Matsuyama	Ehime
Japan	Toranomon Hospital ( Site 3134)	Minato-ku	Tokyo
Japan	Toranomon Hospital ( Site 3153)	Minato-ku	Tokyo
Japan	Kyorin University Hospital ( Site 3103)	Mitaka	Tokyo
Japan	Kyorin University Hospital ( Site 3147)	Mitaka-shi	Tokyo
Japan	Shizuoka Cancer Center ( Site 3128)	Nagaizumi	Shizuoka
Japan	Aichi Cancer Center Hospital ( Site 3101)	Nagoya	Aichi
Japan	National Hospital Organization Nagoya Medical Center ( Site 3109)	Nagoya	Aichi
Japan	Nagoya University Hospital ( Site 3151)	Nagoya-Shi	Aichi
Japan	Miyagi Cancer Center ( Site 3122)	Natori	Miyagi
Japan	University of the Ryukyus Hospital ( Site 3155)	Nishihara	Okinawa
Japan	Hyogo Medical University Hospital ( Site 3100)	Nishinomiya	Hyogo
Japan	Okayama University Hospital ( Site 3107)	Okayama
Japan	National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 31	Osaka
Japan	Osaka City General Hospital ( Site 3125)	Osaka
Japan	Osaka International Cancer Institute-Gynecologic Oncology ( Site 3129)	Osaka
Japan	Kindai University Hospital- Osakasayama Campus ( Site 3166)	Osaka-sayama	Osaka
Japan	Kindai University Hospital ( Site 3102)	Osakasayama	Osaka
Japan	Kindai University Hospital- Osakasayama Campus-Department of Gastroenterology and Hepatology ( Site	Osakasayama	Osaka
Japan	Kitasato University Hospital ( Site 3142)	Sagamihara	Kanagawa
Japan	Osaka Rosai Hospital ( Site 3148)	Sakai	Osaka
Japan	Hokkaido University Hospital ( Site 3165)	Sapporo	Hokkaido
Japan	National Hospital Organization Hokkaido Cancer Center ( Site 3160)	Sapporo	Hokkaido
Japan	Sapporo Kosei General Hospital ( Site 3172)	Sapporo	Hokkaido
Japan	Sapporo Medical University Hospital ( Site 3113)	Sapporo	Hokkaido
Japan	Sendai Kousei Hospital ( Site 3115)	Sendai	Miyagi
Japan	Jichi Medical University Hospital ( Site 3141)	Shimotsuke	Tochigi
Japan	Tokyo Medical University Hospital ( Site 3170)	Shinjuku-ku	Tokyo
Japan	Osaka University Hospital ( Site 3168)	Suita	Osaka
Japan	Osaka Medical and Pharmaceutical University Hospital ( Site 3167)	Takatsuki	Osaka
Japan	Keio University Hospital ( Site 3127)	Tokyo
Japan	National Cancer Center Hospital ( Site 3130)	Tokyo
Japan	Nippon Medical School Hospital ( Site 3139)	Tokyo
Japan	St.Luke's International Hospital ( Site 3120)	Tokyo
Japan	Teikyo University Hospital ( Site 3104)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 3108)	Tokyo
Japan	The Jikei University Hospital-Obstetrics and Gynecology ( Site 3156)	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital ( Site 3133)	Tokyo
Japan	Ehime University Hospital-Obstetrics and Gynecology ( Site 3158)	Toon	Ehime
Japan	National Hospital Organization Yamaguchi Ube Medical Center ( Site 3123)	Ube	Yamaguchi
Japan	Yamaguchi University Hospital ( Site 3114)	Ube	Yamaguchi
Japan	Wakayama Medical University Hospital ( Site 3124)	Wakayama
Japan	Kanagawa cancer center ( Site 3137)	Yokohama	Kanagawa
Japan	Yokohama City University Hospital ( Site 3163)	Yokohama	Kanagawa
Japan	Yokosukakyosai ( Site 3150)	Yokosuka	Kanagawa
Korea, Republic of	Keimyung University Dongsan Hospital CRC room 1 ( Site 0960)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	Chungnam national university hospital-Department of Internal Medicine ( Site 0958)	Daejeon	Taejon-Kwangyokshi
Korea, Republic of	National Cancer Center ( Site 0955)	Goyang-si	Kyonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital-Hemato-Oncology ( Site 0959)	Hwasun	Jeonranamdo
Korea, Republic of	CHA Bundang Medical Center CHA University ( Site 0957)	Seongnam si	Kyonggi-do
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0951)	Seongnam-si	Kyonggi-do
Korea, Republic of	Korea University Anam Hospital ( Site 0956)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 0950)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0953)	Seoul
Korea, Republic of	Severance Hospital ( Site 0954)	Seoul
Korea, Republic of	Asan Medical Center ( Site 0952)	Songpagu	Seoul
Latvia	Liepjas reionl slimnca ( Site 3851)	Liepaja
Latvia	RIGA EAST UNIVERSITY HOSPITAL ,Oncology Centre of Latvia-Out-patient and Day patient facility of Ch	Riga
Lithuania	Klaipeda University Hospital-Oncology chemotherapy ( Site 3302)	Klaipeda	Klaipedos Miestas
Lithuania	National Cancer Institute-Chemotherapy departament with day care unit ( Site 3301)	Vilnius	Vilniaus Miestas
Lithuania	Vilniaus Universiteto Ligonine Santaros Klinikos ( Site 3300)	Vilnius
Malaysia	Gleneagles Penang ( Site 0625)	Georgetown	Pulau Pinang
Malaysia	Pantai Hospital Kuala Lumpur ( Site 0628)	Kuala Lumpur
Malaysia	University Malaya Medical Centre ( Site 0626)	Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan ( Site 0627)	Kuantan	Pahang
Mexico	Oncare Viaducto Napoles ( Site 1107)	Cdmx
Mexico	Medical Care and Research SA de CV ( Site 1103)	Merida	Yucatan
Mexico	INSTITUTO NACIONAL DE CANCEROLOGIA ( Site 1102)	Mexico City	Distrito Federal
Mexico	Avix Investigación Clinica, S.C.-Oncology ( Site 1104)	Monterrey	Nuevo Leon
Mexico	Oaxaca Site Management Organization ( Site 1106)	Oaxaca de Juarez	Oaxaca
Netherlands	Amsterdam UMC, locatie VUmc ( Site 1555)	Amsterdam	Noord-Holland
Netherlands	Antoni van Leeuwenhoek Ziekenhuis ( Site 1551)	Amsterdam	Noord-Holland
Netherlands	Universitair Medisch Centrum Groningen ( Site 1550)	Groningen
Netherlands	Radboud University Medical Center ( Site 1554)	Nijmegen	Gelderland
Netherlands	Erasmus MC ( Site 1553)	Rotterdam	Zuid-Holland
New Zealand	Auckland City Hospital ( Site 1503)	Auckland
New Zealand	Canterbury Regional Cancer & Blood Service ( Site 1500)	Christchurch	Canterbury
New Zealand	Waikato Hospital ( Site 1502)	Hamilton	Waikato
New Zealand	Capital & Coast District Health Board - Wellington Hospital ( Site 1501)	Wellington
Norway	Helse Bergen Haukeland universitetssykehus ( Site 1451)	Bergen	Vestfold
Norway	Oslo Universitetssykehus Radiumhospitalet ( Site 1450)	Oslo
Norway	Oslo Universitetssykehus Ullevål-Avdeling for kreftbehandling, Ullevål ( Site 1452)	Oslo
Peru	Hospital Cayetano Heredia-Oncology ( Site 0675)	Lima
Peru	IPOR Instituto Peruano de Oncología & Radioterapia ( Site 0678)	Lima
Philippines	Makati Medical Center ( Site 1702)	Makati	National Capital Region
Philippines	Lung Center of the Philippines ( Site 1705)	Quezon City	National Capital Region
Philippines	St. Luke s Medical Center ( Site 1700)	Quezon City	National Capital Region
Poland	Bialostockie Centrum Onkologii ( Site 1610)	Bialystok	Podlaskie
Poland	Powiatowe Centrum Zdrowia w Brzezinach Sp. z o. o. Oddzial Dziennej Chemioterapii ( Site 1611)	Brzeziny	Lodzkie
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 1612)	Bydgoszcz	Kujawsko-pomorskie
Poland	Przychodnia Lekarska KOMED ( Site 1603)	Konin	Wielkopolskie
Poland	Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 1614)	Koszalin	Zachodniopomorskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Oddzial w Krakowie ( Site 1608)	Krakow	Malopolskie
Poland	Instytut Centrum Zdrowia Matki Polki-Klinika Onkologii ( Site 1609)	Lódz	Lodzkie
Poland	Opolskie Centrum Onkologii w Opolu im. prof. Tadeusza Kosza-Klinika Onkologii z Odcinkiem Dziennym	Opole	Opolskie
Poland	Med-Polonia Sp. z o. o. ( Site 1605)	Poznan	Wielkopolskie
Poland	Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (	Warszawa	Mazowieckie
Poland	Wojskowy Instytut Medyczny-Klinika Onkologii ( Site 1606)	Warszawa	Mazowieckie
Portugal	Centro Hospitalar Lisboa Norte E.P.E. - Hospital Pulido Valente ( Site 1750)	Lisboa
Portugal	Champalimaud Foundation ( Site 1751)	Lisbon	Lisboa
Portugal	Centro Hospitalar de Sao Joao - Hospital de Sao Joao ( Site 1752)	Porto
Portugal	Instituto Português de Oncologia do Porto Francisco Gentil, EPE-Oncologia Médica ( Site 1753)	Porto
Puerto Rico	Ad-Vance Medical Research-Research ( Site 1151)	Ponce
Puerto Rico	FDI Clinical Research ( Site 1152)	San Juan
Puerto Rico	UPR Comprehensive Cancer Center ( Site 1150)	San Juan
Romania	Spitalul Jude?ean Sfântul Ioan cel Nou Suceava-Oncology ( Site 3550)	Suceava
Russian Federation	Belgorod Oncology Dispensary ( Site 1213)	Belgorod	Belgorodskaya Oblast
Russian Federation	Regional Budgetary Healthcare Institution 'Ivanovo Regional Oncology Dispensary'-Urology ( Site 1219	Ivanovo	Ivanovskaya Oblast
Russian Federation	Udmurtian Republican Clinical Oncology Center ( Site 1212)	Izhevsk	Udmurtskaya Respublika
Russian Federation	Republican Clinical Oncology Dispensary ( Site 1228)	Kazan	Tatarstan, Respublika
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1203)	Kazan	Tatarstan, Respublika
Russian Federation	FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 1208)	Moscow	Moskva
Russian Federation	N.N. Blokhin NMRCO ( Site 1209)	Moscow	Moskva
Russian Federation	P. A. Hertsen Moscow Oncology Research Center ( Site 1214)	Moscow	Moskva
Russian Federation	Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 1201)	Moscow	Moskva
Russian Federation	Russian Scientific Center of Roentgenoradiology ( Site 1215)	Moscow	Moskva
Russian Federation	The National Medico-Surgical Center N.I. Pirogov ( Site 1225)	Moscow	Moskva
Russian Federation	GBUZ SK Pyatigorsk Interdistrict Oncology dispensary ( Site 1223)	Pyatigorsk	Stavropol Skiy Kray
Russian Federation	N.N.Petrov Research Institute of Oncology-Department of Preclinical and Clinical Research ( Site 121	Saint Petersburg	Sankt-Peterburg
Russian Federation	Russian Scientific Research Institute of Hematology and Blood Transfusion-Hematology ( Site 1224)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Clinical Research Center of specialized types medical care-Oncology ( Site 1205)	Saint-Petersburg	Sankt-Peterburg
Russian Federation	GBUZ LOKB ( Site 1218)	Saint-Petersburg	Leningradskaya Oblast
Russian Federation	GBUZ LOKB-Oncology department #1 ( Site 1222)	Saint-Petersburg	Leningradskaya Oblast
Russian Federation	Ogarev Mordovia State University ( Site 1206)	Saransk	Mordoviya, Respublika
Russian Federation	Tomsk Scientific Research Institute of Oncology ( Site 1227)	Tomsk	Tomskaya Oblast
Russian Federation	SAIH of the Tyumen region, Multidisciplinary Clinical Medical Center "Medical town" ( Site 1220)	Tyumen	Tyumenskaya Oblast
Russian Federation	Bashkir State Medical University ( Site 1221)	Ufa	Baskortostan, Respublika
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1204)	Ufa	Baskortostan, Respublika
Singapore	National Cancer Centre Singapore ( Site 2200)	Singapore	Central Singapore
Singapore	National University Hospital-Haematology -Oncology Research Group ( Site 2201)	Singapore	South West
South Africa	Cape Town Oncology Trials ( Site 2007)	Cape Town	Western Cape
South Africa	The Oncology Centre ( Site 2000)	Durban	Limpopo
South Africa	GVI Oncology ( Site 2008)	George	Western Cape
South Africa	Wits Clinical Research ( Site 2002)	Johannesburg	Gauteng
South Africa	LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 2005)	Pretoria	Gauteng
South Africa	Wilgers Oncology Centre ( Site 2006)	Pretoria	Gauteng
South Africa	Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 2004)	Sandton	Gauteng
Spain	Hospital General Universitario de Alicante-Oncologia ( Site 0881)	Alicante
Spain	H.U. Vall de Hebron ( Site 0850)	Barcelona
Spain	Hospital Clinic de Barcelona ( Site 0852)	Barcelona	Cataluna
Spain	Hospital de la Santa Creu i Sant Pau-Oncología Médica ( Site 0862)	Barcelona	Cataluna
Spain	Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 0851)	Barcelona
Spain	Parc de Salut Mar - Hospital del Mar-Oncologia ( Site 0873)	Barcelona
Spain	Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 0860)	Hospitalet de Llobregat	Barcelona
Spain	Complejo Hospitalario de Jaén-Servicio de Oncología Médica ( Site 0879)	Jaen
Spain	Hospital Universitario Insular de Gran Canaria ( Site 0867)	Las Palmas de Gran Canaria	Las Palmas
Spain	Centro Integral Oncologico Clara Campal-Hospital HM Universitario Sanchinarro-START Madrid, ( Site 0	Madrid
Spain	Clinica Universitaria de Navarra ( Site 0855)	Madrid
Spain	Hospital Clinico San Carlos ( Site 0857)	Madrid
Spain	Hospital General Universitario 12 de Octubre ( Site 0856)	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 0871)	Madrid
Spain	Hospital Universitario Gregorio Maranon ( Site 0864)	Madrid
Spain	Hospital Universitario La Paz ( Site 0853)	Madrid
Spain	Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 0877)	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Puerta de Hierro-Majadahonda ( Site 0861)	Majadahonda	Madrid
Spain	Hospital Universitario Virgen de la Victoria ( Site 0878)	Malaga	Andalucia
Spain	H.R.U Malaga - Hospital General ( Site 0884)	Málaga	Malaga
Spain	Hospital Universitario Central de Asturias-Medical Oncology ( Site 0870)	Oviedo	Asturias
Spain	Hospital Universitari Son Espases-Oncologia ( Site 0883)	Palma	Baleares
Spain	Hospital Universitario Quiron Madrid ( Site 0868)	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitari Sant Joan de Reus-Oncology ( Site 0874)	Reus	Tarragona
Spain	H. Marques de Valdecilla ( Site 0865)	Santander	Cantabria
Spain	CHUS - Hospital Clinico Universitario-Servicio de Oncologia ( Site 0876)	Santiago de Compostela	La Coruna
Spain	Hospital Universitario Virgen de Valme-Departamento de Oncologia ( Site 0882)	Sevilla
Spain	HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Medical Oncology ( Site 0872)	Sevilla
Spain	Hospital Universitario Virgen Macarena-Unidad de Investigación Oncológica ( Site 0880)	Sevilla
Spain	Hospital Arnau de Vilanova ( Site 0866)	Valencia	Valenciana, Comunitat
Spain	Hospital Clinico de Valencia ( Site 0858)	Valencia	Valenciana, Comunitat
Spain	Hospital General Universitario de Valencia ( Site 0854)	Valencia	Valenciana, Comunitat
Spain	Instituto Valenciano de Oncologia - IVO ( Site 0863)	Valencia	Valenciana, Comunitat
Spain	Hospital Universitari i Politecnic La Fe ( Site 0875)	València	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa ( Site 0859)	Zaragoza
Sweden	Sahlgrenska Universitetssjukhuset-Department of Oncology CTU Clinical Trial Unit ( Site 0803)	Gothenburg	Vastra Gotalands Lan
Sweden	Karolinska Universitetssjukhuset Solna ( Site 0802)	Stockholm	Stockholms Lan
Sweden	Norrlands Universitetssjukhus ( Site 0800)	Umea	Vasterbottens Lan
Sweden	Blod och Tumorssjukdomar. Akademiska sjukhuset ( Site 0801)	Uppsala	Uppsala Lan
Switzerland	University Hospital Basel ( Site 0752)	Basel	Basel-Stadt
Switzerland	Hôpitaux Universitaires de Genève (HUG) ( Site 0753)	Genève	Geneve
Switzerland	Universitaetsspital Zuerich ( Site 0750)	Zürich-Flughafen	Zurich
Taiwan	Kaohsiung Chang Gung Memorial Hospital ( Site 3203)	Kaohsiung
Taiwan	China Medical University Hospital ( Site 3204)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 3201)	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center-Gynecology, Obstetrics, and women's health ( Site 3207)	Taipei
Taiwan	Mackay Memorial Hospital ( Site 3205)	Taipei
Taiwan	National Taiwan University Hospital ( Site 3200)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 3202)	Taipei
Taiwan	Chang Gung Medical Foundation-Linkou Branch ( Site 3206)	Taoyuan
Thailand	Chulalongkorn University ( Site 2363)	Bangkok	Krung Thep Maha Nakhon
Thailand	Faculty of Medicine Siriraj Hospital ( Site 2365)	Bangkok	Krung Thep Maha Nakhon
Thailand	Ramathibodi Hospital ( Site 2364)	Bangkok	Krung Thep Maha Nakhon
Turkey	Acibadem Adana Hospital-Pediatric Hematology-Oncology ( Site 1312)	Adana
Turkey	Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 1307)	Adana
Turkey	Ankara City Hospital-Medical Oncology ( Site 1311)	Ankara
Turkey	Ankara University Hospital Cebeci ( Site 1306)	Ankara
Turkey	Baskent Universitesi Ankara Hastanesi ( Site 1303)	Ankara
Turkey	Hacettepe Universitesi-oncology hospital ( Site 1304)	Ankara
Turkey	Memorial Antalya Hospital-Oncology ( Site 1315)	Antalya
Turkey	Trakya Universitesi Tip Fakultesi ( Site 1301)	Edirne
Turkey	Bezmialem Vakf Üniversitesi-Oncology ( Site 1308)	Istanbul
Turkey	Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1302)	Istanbul
Turkey	Istanbul University Capa Campus ( Site 1314)	Istanbul
Turkey	Marmara Universitesi Pendik Egitim Arastirma Hastanesi-Medical Oncology ( Site 1305)	Istanbul
Turkey	TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1316)	Istanbul
Turkey	Ege Universitesi Tip Fakultesi Hastanesi ( Site 1300)	Izmir
Turkey	I.E.U. Medical Point Hastanesi-Oncology ( Site 1310)	Izmir
Turkey	Kocaeli Üniversitesi ( Site 1313)	Kocaeli
Turkey	Inonu Universitesi ( Site 1309)	Malatya
Turkey	Acibadem Altunizade Hospital-Oncology ( Site 1317)	Üsküdar /Istanbul	Istanbul
Ukraine	Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council ( Site 3650)	Dnipro	Dnipropetrovska Oblast
Ukraine	Communal Non-Commercial Enterprise "Prykarpatski Clinical Oncological Center" of Ivano-Frankivsk Reg	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	MNPE Regional Center of Oncology ( Site 3665)	Kharkiv	Kharkivska Oblast
Ukraine	Private Enterprise Private Manufacturing Company Acinus-Medical and Diagnostic Centre ( Site 3656)	Kropyvnytskyi	Kirovohradska Oblast
Ukraine	MI Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional-Chemotherapy department ( Site 3657)	Kryvyi Rih	Dnipropetrovska Oblast
Ukraine	Municipal non-profit enterprise "Kyiv City Clinical Oncology Center" of executive body of Kyiv City	Kyiv	Kyivska Oblast
Ukraine	National Cancer Institute-Department of Minimally Invasive and Endoscopic Surgery, Interventional R	Kyiv	Kyivska Oblast
Ukraine	Municipal institution of Lviv regional council Lviv Oncology-Chemotherapy ( Site 3653)	Lviv	Lvivska Oblast
Ukraine	Odessa Regional Oncology Center ( Site 3655)	Odessa	Odeska Oblast
Ukraine	Sumy regional clinical oncological dispensary-Oncothoracic department ( Site 3661)	Sumy	Sumska Oblast
Ukraine	Transcarpathian Regional Clinical Oncology Center-Chemotherapy dept. ( Site 3652)	Uzhhorod	Zakarpatska Oblast
Ukraine	Communal Noncommercial Enterprise "Podillia Regional Oncology Center Of Vinnytsia Regional Council"	Vinnytsia	Vinnytska Oblast
Ukraine	Municipal non-profit enterprise "Zaporizhzhia Regional Antitumor Center" Zaporizhzhya Regional Counc	Zaporizhia	Zaporizka Oblast
United Kingdom	Aberdeen Royal Infirmary-Department of Oncology ( Site 0521)	Aberdeen	Aberdeen City
United Kingdom	Belfast City Hospital ( Site 0508)	Belfast	Northern Ireland
United Kingdom	Mid Essex Hospitals Service Trust. Broomfield Hospital ( Site 0503)	Broomfield	Essex
United Kingdom	Western General Hospital ( Site 0502)	Edinburgh	Edinburgh, City Of
United Kingdom	The Beatson West of Scotland Cancer Centre ( Site 0506)	Glasgow	Glasgow City
United Kingdom	St James University Hospital ( Site 0509)	Leeds
United Kingdom	Barts Health NHS Trust ( Site 0512)	London	London, City Of
United Kingdom	Royal Free Hospital ( Site 0507)	London	London, City Of
United Kingdom	Royal Marsden Hospital ( Site 0505)	London	London, City Of
United Kingdom	Sarah Cannon Research UK ( Site 0504)	London	London, City Of
United Kingdom	University College London Hospital-Cancer Clinical Trials Unit ( Site 0520)	London	London, City Of
United Kingdom	The Christie ( Site 0516)	Manchester	England
United Kingdom	Nottingham University Hospitals NHS Trust ( Site 0510)	Nottingham	Nottinghamshire
United Kingdom	Royal Preston Hospital ( Site 0518)	Preston	Lancashire
United Kingdom	Weston Park Hospital ( Site 0519)	Sheffield	England
United Kingdom	The Royal Marsden NHS Foundation Trust. ( Site 0513)	Sutton
United Kingdom	New Cross Hospital-Department of Oncology ( Site 0517)	Wolverhampton
United States	Emory School of Medicine ( Site 0013)	Atlanta	Georgia
United States	University of Colorado Cancer Center ( Site 0021)	Aurora	Colorado
United States	Comprehensive Blood & Cancer Center [Bakersfield, CA] ( Site 0054)	Bakersfield	California
United States	MedStar Franklin Square Medical Center ( Site 0046)	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0056)	Baltimore	Maryland
United States	St. Luke's University Health Network ( Site 0017)	Bethlehem	Pennsylvania
United States	Dana-Farber Cancer Institute ( Site 0006)	Boston	Massachusetts
United States	Massachusetts General Hospital ( Site 0041)	Boston	Massachusetts
United States	WakeMed Cancer Care - Waverly Hematology & Medical Oncology ( Site 0074)	Cary	North Carolina
United States	University of North Carolina at Chapel Hill ( Site 0040)	Chapel Hill	North Carolina
United States	Levine Cancer Institute ( Site 0034)	Charlotte	North Carolina
United States	University of Virginia Health System ( Site 0035)	Charlottesville	Virginia
United States	The University of Chicago ( Site 0020)	Chicago	Illinois
United States	University Hospitals ( Site 0044)	Cleveland	Ohio
United States	Texas Oncology-Baylor Sammons Cancer Center ( Site 0062)	Dallas	Texas
United States	Karmanos Cancer Institute ( Site 0047)	Detroit	Michigan
United States	Duke Cancer Center ( Site 0028)	Durham	North Carolina
United States	Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0065)	Fargo	North Dakota
United States	Holy Cross Hospital, Michael & Dianne Bienes Comp Cancer Ctr ( Site 0022)	Fort Lauderdale	Florida
United States	California Cancer Associates for Research & Excellence ( Site 0016)	Fresno	California
United States	West Cancer Center and Research Institute ( Site 0055)	Germantown	Tennessee
United States	John Theurer Cancer Center at Hackensack University Medical Center ( Site 0038)	Hackensack	New Jersey
United States	Kaiser Permanente Moanalua Medical Center ( Site 0063)	Honolulu	Hawaii
United States	University of Texas MD Anderson Cancer Center ( Site 0007)	Houston	Texas
United States	University of Iowa Hospital and Clinics ( Site 0026)	Iowa City	Iowa
United States	Comprehensive Cancer Centers of Nevada ( Site 0043)	Las Vegas	Nevada
United States	The Angeles Clinic and Research Institute ( Site 0005)	Los Angeles	California
United States	UCLA Hematology/Oncology - Westwood (Building 100) ( Site 0009)	Los Angeles	California
United States	James Graham Brown Cancer Center ( Site 0058)	Louisville	Kentucky
United States	Northwest Georgia Oncology Centers PC ( Site 0061)	Marietta	Georgia
United States	Mount Sinai Medical Center Comprehensive Cancer Center ( Site 0031)	Miami Beach	Florida
United States	Bon Secours St. Francis Medical Center-Oncology Research ( Site 0075)	Midlothian	Virginia
United States	Vanderbilt Health One Hundred Oaks Diagnostic ( Site 0060)	Nashville	Tennessee
United States	Vanderbilt Ingram Cancer Center ( Site 0015)	Nashville	Tennessee
United States	Cancer Institute of New Jersey ( Site 0025)	New Brunswick	New Jersey
United States	Yale Cancer Center ( Site 0014)	New Haven	Connecticut
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0032)	New York	New York
United States	Memorial Sloan Kettering Cancer Center ( Site 0012)	New York	New York
United States	Fox Chase Cancer Center ( Site 0042)	Philadelphia	Pennsylvania
United States	University of Pennsylvania ( Site 0010)	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center ( Site 0008)	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center ( Site 0051)	Portland	Oregon
United States	Blue Ridge Cancer Care ( Site 0067)	Roanoke	Virginia
United States	Mayo Clinic in Rochester, Minnesota ( Site 0002)	Rochester	Minnesota
United States	South Texas Accelerated Research Therapeutics, LLC (START) ( Site 0001)	San Antonio	Texas
United States	UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0004)	San Francisco	California
United States	Providence Saint John's Health Center ( Site 0059)	Santa Monica	California
United States	Seattle Cancer Care Alliance ( Site 0024)	Seattle	Washington
United States	Sanford Cancer Center ( Site 0066)	Sioux Falls	South Dakota
United States	Moffitt Cancer Center ( Site 0011)	Tampa	Florida
United States	University of Arizona Cancer Center ( Site 0018)	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0082)	Tulsa	Oklahoma
United States	Georgetown University Medical Center ( Site 0023)	Washington	District of Columbia
United States	White Plains Hospital-Center for Cancer Care ( Site 0069)	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Guatemala,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Peru,  Philippines,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

Robert C, Carlino MS, McNeil C, Ribas A, Grob JJ, Schachter J, Nyakas M, Kee D, Petrella TM, Blaustein A, Lotem M, Arance A, Daud AI, Hamid O, Larkin J, Anderson J, Krepler C, Grebennik D, Long GV. Seven-Year Follow-Up of the Phase III KEYNOTE-006 Study: — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is defined as the time from randomization or start of study treatment for non-randomized participants (on the parent study) to death due to any cause. Participants without documented death at the time of analysis will be censored at the date of the last follow-up.	Up to approximately 10 years
Secondary	Duration of Response (DOR) Per Evaluation Criteria Used in the Parent Study	DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response on the parent study until earliest date of disease progression or death from any cause, whichever comes first based upon investigator assessment. The DOR will be presented.	Up to approximately 10 years
Secondary	Duration of Complete Response (DOCR) Per Evaluation Criteria Used in the Parent Study	DOCR is determined by disease assessment and is defined as the time from the date of complete response (CR) on the parent study until earliest date of disease progression or death from any cause, whichever comes first based upon investigator assessment. The DOCR will be presented.	Up to approximately 10 years
Secondary	Number of Participants Who Experience Serious Adverse Events (SAEs)	A SAE is defined as any untoward medical occurrence that, at any dose: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity or Is a congenital anomaly/birth defect. The number of participants who experience a SAE in this study will be presented.	Up to approximately 42 months (Up to 90 days after last dose of study treatment)
Secondary	Number of Participants Who Experience Adverse Events of Special Interest (AEOSI)	AEOSI for this study include selected preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 20.1 for the following higher-level terms: Pneumonitis, Colitis, Hepatitis, Nephritis, Adrenal Insufficiency, Hypophysitis, Hyperthyroidism, Hypothyroidism, Thyroiditis, Type 1 Diabetes Mellitus, Severe Skin Reactions Including Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): or If grade 3 or higher, Uveitis, Pancreatitis, Myositis, Guillain-Barre Syndrome, Myocarditis, Encephalitis, Sarcoidosis, Infusion Reactions and Myasthenic Syndrome. The number of participants who experience an AEOSI in this study will be presented.	Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Secondary	Number of Participants Who Experience Clinically Significant Adverse Events (CSAE)	CSAE are AEs associated with lenvatinib treatment and include selected preferred terms from the lenvatinib CSAE preferred term list document. The number of participants who experience an CSAE in this study will be presented.	Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Secondary	Number of Participants Who Experience Events of Clinical Interest (ECI)	ECIs for this study include: 1) An overdose of Sponsor's product, that is not associated with clinical symptoms or abnormal laboratory results or 2) An elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is =3X the upper limit of normal (ULN) and an elevated total bilirubin lab value that is =2X ULN and, at the same time, an alkaline phosphatase lab value that is <2X ULN, as determined by way of protocol-specified laboratory testing or unscheduled laboratory testing. The number of participants who experience an ECI in this study will be presented.	Up to approximately 40 months (Up to 30 days after last dose of study treatment)
Secondary	Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 39 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary