A Study of Vemurafenib in Participants With Metastatic Melanoma

Phase 3

Completed

Conditions: Malignant Melanoma

Interventions: Drug: Vemurafenib

Registration Number: NCT01307397

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This multi-center study evaluates the safety and efficacy of vemurafenib in participants with BRAF V600 mutation-positive, surgically incurable, and unresectable Stage IIIC or IV (American Joint Committee on Cancer \[AJCC\]) metastatic melanoma.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3219

Inclusion Criteria

Participants with Histologically confirmed metastatic melanoma (surgically incurable and unresectable Stage IIIC or Stage IV; AJCC) with BRAF V 600 mutation determined by Cobas 4800 BRAF Mutation Test. Unresectable Stage IIIC disease must have had confirmation from a surgical oncologist
Participants with either measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
Participants may or may not have received prior systemic therapy for metastatic melanoma
Eastern Cooperative Oncology Group (ECOG) performance status between 0 to 2
Adequate hematologic, renal and liver function

Exclusion Criteria

Evidence of symptomatic central nervous system (CNS) lesions, use of steroids or anti-seizure medications for treatment of brain metastases prior to the first administration of vemurafenib
Previous malignancy (other than melanoma) within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix
Concurrent administration of any anti-cancer therapies other than those administered in the study
Clinically significant cardiovascular disease or event within the 6 months prior to first administration of study drug
Refractory nausea or vomiting, external biliary shunt, or significant bowel resection that would preclude adequate absorption

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vemurafenib	Vemurafenib	Participants will receive vemurafenib at a dose of 960 milligrams (mg) twice daily (bid) until the development of progressive disease, unacceptable toxicity, consent withdrawal, protocol violations endangering participant's safety, death, or study termination by the Sponsor, whichever occurs first.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Any Grade 3 or 4 Adverse Events (AEs) as Determined by National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.0	Baseline up to 28 days post end of treatment (maximum up to 46 months)	The intensity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the NCI-CTCAE version 4.0, where Grade 1 indicates "Mild" severity and Grade 5 indicates "Death". The CTCAE defines Grades 3 and 4 as follows: Grade 3 means "Severe"; Inability to work or perform normal daily activity; treatment or medical intervention is indicated in order to improve the overall well-being or symptoms; delaying the onset of treatment is not putting the survival of the participant at direct risk. Grade 4 means "Life-threatening, Disabling"; based on extreme limitation in activity; significant medical intervention/therapy required; and hospitalization probable.
Mean Cumulative Dose of Vemurafenib	Baseline up to end of treatment or death (maximum up to 46 months)
Duration of Vemurafenib Treatment	Baseline up to end of treatment or death (maximum upto 46 months)	Exposure excluding treatment interruptions: Duration during which participants actually took vemurafenib. Any time without dose-taken due to adverse events, non-compliance or any other reasons was not counted. Exposure including treatment interruptions: date of last dose - date of first dose + 1; duration during which participants actually took vemurafenib as well as duration on which medication was not taken were included in this calculation.
Percentage of Participants With AEs of Special Interest	Baseline up to 28 days post end of treatment (maximum up to 46 months)	AEs of special interest included cutaneous squamous cell carcinoma (SCC), rash, photosensitivity, liver injury, arthralgia, fatigue, gastrointestinal (GI) polyps, pancreatitis, potentiation of radiation toxicity, prolongation of cardiac repolarization or arrhythmia, non-cutaneous SCC and other primary malignancies (other than cutaneous SCC or new primary melanoma).
Percentage of Participants With at Least 1 AE Leading to Study Drug Interruption or Drug Discontinuation	Baseline up to 28 days post end of treatment (maximum up to 46 months)	An AE was considered as any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Pre existing conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. Percentage of participants with dose interruption or discontinuation due to AE was presented.
Mean Total Vemurafenib Dose Per Day	Baseline up to end of treatment or death (maximum up to 46 months)	Exposure excluding treatment interruptions: Duration during which participants actually took vemurafenib. Any time without dose-taken due to adverse events, non-compliance or any other reasons was not counted. Exposure including treatment interruptions: date of last dose - date of first dose + 1; duration during which participants actually took vemurafenib as well as duration on which medication was not taken were included in this calculation. Average total dose per day: total actual dose taken divided by total actual days on treatment.
Dose Intensity of Vemurafenib	Baseline up to end of treatment or death (maximum upto 46 months)	Dose intensity was defined as (total actual doses taken/total planned doses) \100, where total planned doses = prescribed doses \ planned days on treatment, where planned days on treatment were defined as the interval between date of first dose and date of last dose.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR), as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Baseline until first documentation of confirmed CR or PR (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])	BOR was assessed by the investigator according to RECIST v1.1. BOR was defined as having confirmed CR or PR. CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to less than (\<) 10 millimeter (mm) in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging greater than or equal to (\>=) 4 weeks after initial response.
Percentage of Participants With Improvement in Eastern Cooperative Group (ECOG) Performance Status	Baseline, Day 1 of each 28 day cycle up to end of treatment (up to 46 months)	ECOG Performance Status was measured on-therapy assessed participant's performance status on 5 point scale: 0 = fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than \[\>\] 50% of waking hours \[hrs\]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair \>50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. Percentage of participants who had at least one point improvement from baseline at any assessment visit as well as at last study visit was reported.
Percentage of Participants Who Received Any Concomitant Medications	Baseline up to 46 months	Concomitant medications were all medications taken during the study, including those started before but ongoing at first dose. No medications for Melanoma were included. Percentage of participants who received at least one concomitant medication was reported.
Percentage of Participants With PD Assessed According to RECIST v1.1 or Death	Baseline until PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])	PD was assessed according to RECIST v1.1. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.
Duration of Response	From 1st documentation of confirmed CR or PR to PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until end of the study [up to 46 months])	The duration of response was defined as the time between the date of first confirmed CR or PR and date of first progression of disease (PD), or death, from any cause. Responses were assessed as per RECIST v1.1. CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \< 10 mm in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging \>= 4 weeks after initial response. PD: at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.
Progression Free Survival (PFS)	Baseline until PD or death, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])	PFS was defined as the time between the date of the first treatment and the date of first progression or death from any cause. PD was assessed according to RECIST v1.1. PD was defined as at least 20% increase in the sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesion.
Time to Response	Baseline until first documentation of confirmed CR or PR, whichever occurred first (assessed at baseline, at Weeks 8, 16, as per institution standard of care thereafter but a minimum every 16 weeks thereafter until the end of the study [up to 46 months])	Time to response was defined as the time between the date of first treatment and date of first confirmed CR or PR (assessed as per RECIST v1.1). CR: disappearance of all target and non-target lesions and no new lesions, all pathological lymph nodes must have decreased to \< 10 mm in short axis; PR: at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesion, and no new lesions. Confirmed responses were those that persisted on repeat imaging \>= 4 weeks after initial response.
Percentage of Participants Who Died	Baseline until death (maximum up to 46 months)
Overall Survival (OS)	Baseline until death (maximum up to 46 months)	Overall Survival was defined as the time from the date of first treatment to the date of death, regardless of the cause of death.

Trial Locations

Locations (280): University "Mother Theresa" Hospital Center; Oncology Department
🇦🇱
Tirana, Albania
Hospital Britanico; Oncologia
🇦🇷
Buenos Aires, Argentina
Fundación CIDEA
🇦🇷
Buenos Aires, Argentina
Westmead Hospital
🇦🇺
Westmead, New South Wales, Australia
Newcastle Mater Misericordiae Hospital; Oncology
🇦🇺
Waratah, New South Wales, Australia
Border Medical Oncology
🇦🇺
Wodonga, New South Wales, Australia
Greenslopes Private Hospital; Gallipoli Research Centre
🇦🇺
Greenslopes, Queensland, Australia
The Townsville Hospital; Townsville Cancer Centre
🇦🇺
Townsville, Queensland, Australia
Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology
🇦🇺
Woolloongabba, Queensland, Australia
Peter MacCallum Cancer Centre; Medical Oncology
🇦🇺
Melbourne, Victoria, Australia
Geelong Hospital; Geelong Cardiology Practice
🇦🇺
Geelong, Victoria, Australia
Landeskrankenhaus Feldkirch; Abteilung für Innere Medizin
🇦🇹
Feldkirch, Austria
LKH Graz; Abteilung für allgemeine Dermatologie
🇦🇹
Graz, Austria
LKH Innsbruck; Universitätsklinik für Dermatologie
🇦🇹
Innsbruck, Austria
Krankenhaus der Elisabethinen Linz; Abteilung für Dermatologie
🇦🇹
Linz, Austria
LKH Salzburg; Universitätsklinik für Dermatologie
🇦🇹
Salzburg, Austria
Landesklinikum St. Pölten
🇦🇹
St. Pölten, Austria
Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.
🇦🇹
Salzburg, Austria
UZ Brussel
🇧🇪
Brussel, Belgium
Sint Augustinus Wilrijk
🇧🇪
Wilrijk, Belgium
Cliniques Universitaires St-Luc
🇧🇪
Bruxelles, Belgium
Clinic of Oncology, University Clinical Center Sarajevo
🇧🇦
Sarajevo, Bosnia and Herzegovina
University Clinical Center of the Republic of Srpska
🇧🇦
Banja Luka, Bosnia and Herzegovina
Instituto Nacional de Cancer - INCa; Pesquisa Clinica
🇧🇷
Rio de Janeiro, RJ, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷
Sao Paulo, SP, Brazil
Hospital das Clinicas - UFRGS
🇧🇷
Porto Alegre, RS, Brazil
Hospital A. C. Camargo; Oncologia
🇧🇷
Sao Paulo, SP, Brazil
District Oncology Dispensary; Department for Oncology and Dermatology
🇧🇬
Plovdiv, Bulgaria
National Specialized Hospital for Active Oncology Treatment; Dermatology Clinic
🇧🇬
Sofia, Bulgaria
Cross Cancer Institute ; Dept of Medical Oncology
🇨🇦
Edmonton, Alberta, Canada
Lion'S Gate Hospital
🇨🇦
North Vancouver, British Columbia, Canada
British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
🇨🇦
Vancouver, British Columbia, Canada
QEII HSC; Oncology
🇨🇦
Halifax, Nova Scotia, Canada
Hamilton Health Sciences - Juravinski Cancer Centre
🇨🇦
Hamilton, Ontario, Canada
London Regional Cancer Centre
🇨🇦
London, Ontario, Canada
The Ottawa Hospital; Division of Infectious Diseases
🇨🇦
Ottawa, Ontario, Canada
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
🇨🇦
Montreal, Quebec, Canada
Chuq - Hopital Hotel Dieu de Quebec; Oncology
🇨🇦
Quebec City, Quebec, Canada
Fundacion Santa Fe de Bogotá
🇨🇴
Bogota, Colombia
Centro Javeriano de Oncología
🇨🇴
Bogota, Colombia
Hospital Pablo Tobon Uribe
🇨🇴
Medellin-Antioquia, Colombia
Clínica Imbanaco; Oncology
🇨🇴
Cali, Colombia
Clinical Hospital Sisters of Mercy
🇭🇷
Zagreb, Croatia
Masarykův onkologický ústav; Klinika komplexní onkologické péče
🇨🇿
Brno, Czechia
Faculty Hospital; Dialysis Unit
🇨🇿
Ostrava, Czechia
University Hospital; Oncology and Radiotherapy
🇨🇿
Hradec Kralove, Czechia
Fakultni nemocnice Olomouc; Onkologicka klinika
🇨🇿
Olomouc, Czechia
1 Lekarska Fakulta Uni Karlovy; 3 Interni Klinika, Labor. Pro Endokrinologii A Metabolismus
🇨🇿
Praha, Czechia
Faculty Hospital Kralovske Vinohrady; Oncology
🇨🇿
Praha, Czechia
Aarhus Universitetshospital; Kræftafdelingen
🇩🇰
Aarhus C, Denmark
Herlev Hospital; Onkologisk afdeling
🇩🇰
Herlev, Denmark
Odense Universitetshospital, Onkologisk Afdeling R
🇩🇰
Odense, Denmark
Hospital Regional Vicente Corral Moscoso, Servicio de Oncología
🇪🇨
Cuenca, Ecuador
Hospital Abel Gilbert Ponton; Oncology
🇪🇨
Guayaquil, Ecuador
Hospital Solca Portoviejo; Oncologia
🇪🇨
Portoviejo, Ecuador
North Estonia Medical Centre Foundation; Oncology Center
🇪🇪
Tallinn, Estonia
Tartu University Hospital; Clinic of Hematology and Oncology
🇪🇪
Tartu, Estonia
Tampere University Hospital; Dept of Oncology
🇫🇮
Tampere, Finland
Turku Uni Central Hospital; Oncology Clinics
🇫🇮
Turku, Finland
Helsinki University Central Hospital; Dept of Oncology
🇫🇮
Helsinki, Finland
Uniklinik RWTH Aachen; Klinik für Dermatologie und Allergologie - Hautklinik
🇩🇪
Aachen, Germany
Klinikum Augsburg Süd; Klinik für Dermatologie und Allergologie
🇩🇪
Augsburg, Germany
CAMPUS BENJAMIN FRANKLIN CharitéCentrum 14 Med.Klinik f.Hämatologie u.Onkologie
🇩🇪
Berlin, Germany
St. Josef-Hospital Klinik f. Dermatologie u. Allergologie
🇩🇪
Bochum, Germany
Elbekliniken Buxtehude; Klinik für Dermatologie
🇩🇪
Buxtehude, Germany
DRK-Krankenhaus; Hautklinik
🇩🇪
Chemnitz, Germany
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I
🇩🇪
Dresden, Germany
Universitätsklinikum Düsseldorf; Hautklinik
🇩🇪
Düsseldorf, Germany
Universitätsklinikum Erlangen; Hautklinik
🇩🇪
Erlangen, Germany
HELIOS Klinikum Erfurt, Klinik für Hautkrankheiten und Allergologie
🇩🇪
Erfurt, Germany
Universitätsklinikum Essen
🇩🇪
Essen, Germany
Klinik Johann Wolfgang von Goethe Uni; Klinik fuer Allgemein- und Viszeralchirurgie
🇩🇪
Frankfurt, Germany
Uniklinikum Freiburg Dermatol
🇩🇪
Freiburg, Germany
Universitätsmedizin Göttingen Georg-August-Universität Zentrum Dermatologie
🇩🇪
Göttingen, Germany
Universitätsklinikum Hamburg-Eppendorf Zentrum f.Innere Medizin Klinik f.Dermatologie
🇩🇪
Hamburg, Germany
SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
🇩🇪
Gera, Germany
Medizinische Hochschule; Hautklinik Linden
🇩🇪
Hannover, Germany
Klinikum Kassel; Hautklinik
🇩🇪
Kassel, Germany
Uni-Hautklinik
🇩🇪
Heidelberg, Germany
Klinik der Uni zu Köln; Klinik & Poliklinik fuer Dermatologie & Venerologie
🇩🇪
Köln, Germany
Klinikum am Gesundbrunnen; Tumorzentrum
🇩🇪
Heilbronn, Germany
Universitätsklinikum Jena; Klinik für Hautkrankheiten
🇩🇪
Jena, Germany
UNI-Klinikum Campus Kiel Klinik f.Dermatologie Tagesklinik f.Dermatologie
🇩🇪
Kiel, Germany
Universitätsklinikum Leipzig Klinik f.Dermatologie Venerologie u.Allergologie
🇩🇪
Leipzig, Germany
Klinikum d.Stadt Ludwigshafen Hautklinik
🇩🇪
Ludwigshafen, Germany
Universitätsklinikum Magdeburg; Hautklinik; Klinik für Dermatologie und Venerologie
🇩🇪
Magdeburg, Germany
Johannes Gutenberg Unis-Klinik; Dept For Dermatology
🇩🇪
Mainz, Germany
Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie
🇩🇪
Mannheim, Germany
Universitätsklinikum Marburg Klinik f. Dermatologie
🇩🇪
Marburg, Germany
Klinikum der LMU München; Klinik und Poliklinik für Dermatologie und Allergologie
🇩🇪
München, Germany
Johannes-Wesling-Klinikum Minden; Onkologische Ambulanz / Tagesklinik
🇩🇪
Minden, Germany
Universitätsklinikum Münster
🇩🇪
Münster, Germany
Staedtisches Krankenhaus Muenchen-Schwabing, Haematologie & Onkolgie
🇩🇪
München, Germany
Fachklinik Hornheide; Internistische Onkologie
🇩🇪
Münster, Germany
Klinikum Nürnberg Nord; Hautklinik; Klinik für Dermatologie
🇩🇪
Nürnberg, Germany
Universitätsklinikum Regensburg; Klinik und Poliklinik für Dermatologie
🇩🇪
Regensburg, Germany
Klinikum Dorothea Ch.Erxleben; Klinik für Dermatologie und Allergologie
🇩🇪
Quedlinburg, Germany
KLINIKUM VEST GmbH Knappschaftskrankenhaus Abt.Haut- Allergie- Venen- und Umwelterkrankungen
🇩🇪
Recklinghausen, Germany
Universitaets-Hautklinik Tuebingen
🇩🇪
Tübingen, Germany
Wilhelm Fresenius Klinik; Klinik f. Dermatologie u. Allergologie
🇩🇪
Wiesbaden, Germany
Universitätsklinikum Würzburg; Klinik und Poliklinik für Dermatologie Venerologie u. Allergologie
🇩🇪
Würzburg, Germany
HELIOS Klinikum Barmen Zentrum Dermatologie Allergologie und Umweltmedizin
🇩🇪
Wuppertal, Germany
Laiko General Hospital; 1St Pathological Clinic
🇬🇷
Athens, Greece
Debreceni Egyetem OEC; Borgyogyaszati Klinika
🇭🇺
Debrecen, Hungary
Metropolitan Hospital; Dept. of Oncology
🇬🇷
Piraeus, Greece
Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly
🇭🇺
Budapest, Hungary
Szegedi Tud.Egyetem Szent-Gyorgyi Albert Klin.Kozp.
🇭🇺
Szeged, Hungary
Pecsi Tudomanyegyetem AOK; Borgyogyaszati Klinika
🇭🇺
Pecs, Hungary
Basavatarakam Indo-American Cancer Hospital & Research Institute
🇮🇳
Hyderabad, India
Curie Manavata Cancer Centre
🇮🇳
Nashik, Maharashtra, India
Chhatrapati Shahuji Maharaj Medical University; Department of Oncology
🇮🇳
Lucknow, India
Christian Med Clg & Hspt
🇮🇳
Vellore, India
Regional Cancer Centre; Dept of Oncology
🇮🇳
Trivandrum, India
Cork Uni Hospital; Oncology Dept
🇮🇪
Cork, Ireland
St Vincent'S Uni Hospital; Medical Oncology
🇮🇪
Dublin, Ireland
Mater Misericordiae Uni Hospital; Oncology
🇮🇪
Dublin, Ireland
Mater Private Hospital
🇮🇪
Dublin, Ireland
St James' Hospital; Cancer Clinical Trials Office
🇮🇪
Dublin, Ireland
Galway Uni Hospital; Oncology Dept
🇮🇪
Galway, Ireland
University Hospital Limerick - Oncology
🇮🇪
Limerick, Ireland
Waterford Regional Hospital; Department Of Medical Oncology
🇮🇪
Waterford, Ireland
Soroka Medical Center; Oncology Dept
🇮🇱
Beer Sheva, Israel
Hadassah Ein Karem Hospital; Oncology Dept
🇮🇱
Jerusalem, Israel
Chaim Sheba Medical Center; Oncology Dept
🇮🇱
Ramat Gan, Israel
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
🇮🇹
Meldola, Emilia-Romagna, Italy
Istituto Dermopatico dell'Immacolata (IDI)-IRCCS; IV Divisione Oncologica e Dermatologia Oncologica
🇮🇹
Roma, Lazio, Italy
IFO - Istituto Regina Elena; Oncologia Medica
🇮🇹
Roma, Lazio, Italy
Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
🇮🇹
Milano, Lombardia, Italy
IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
🇮🇹
Genova, Liguria, Italy
Seoul St Mary's Hospital
🇰🇷
Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda
🇮🇹
Padova, Veneto, Italy
Seoul National University Hosp; Dept Internal Med Hem Onc
🇰🇷
Seoul, Korea, Republic of
Yonsei University Severance Hospital; Medical Oncology
🇰🇷
Seoul, Korea, Republic of
Asan Medical Center.
🇰🇷
Seoul, Korea, Republic of
Daugavpils Regional Hospital
🇱🇻
Daugavpils, Latvia
Inst. Nacional de Cancerologia; Investigacion Clinica
🇲🇽
Mexico City, Mexico
Klaipeda University Hospital
🇱🇹
Klaipeda, Lithuania
Vilnius University Hospital Santariskiu Clinic, Hematology, Oncology and Tranfusion Medicine Center
🇱🇹
Vilnius, Lithuania
University Clinic for Radiotherapy and Oncology Skopje; Department of skin malignancies
🇲🇰
Skopje, Macedonia, The Former Yugoslav Republic of
Fundación Rodolfo Padilla Padilla, A.C.; Oncology
🇲🇽
Leon, Mexico
Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde
🇳🇱
Amsterdam, Netherlands
Tergooiziekenhuizen
🇳🇱
Blaricum, Netherlands
VU MEDISCH CENTRUM; Dept. of Medical Oncology
🇳🇱
Amsterdam, Netherlands
Hospital General de México; Unidad de Oncologia
🇲🇽
Mexico DF, Mexico
Amphia Ziekenhuis
🇳🇱
Breda, Netherlands
Academisch Ziekenhuis Leiden; Clinical Oncology
🇳🇱
Leiden, Netherlands
Academ Ziekenhuis Groningen; Medical Oncology
🇳🇱
Groningen, Netherlands
Academish Ziekenhuis Maastricht (Azm); Inwendige Geneeskunde
🇳🇱
Maastricht, Netherlands
UMC St Radboud; Interne Oncologie; Medical Oncology Department
🇳🇱
Nijmegen, Netherlands
Erasmus MC
🇳🇱
Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht; Inwendige Geneeskunde Afd.
🇳🇱
Utrecht, Netherlands
Instituto Nacional de Enfermedades Neoplasicas
🇵🇪
Lima, Peru
Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology
🇵🇪
Arequipa, Peru
Haukeland Universitetshospital; Onkologisk Avd.
🇳🇴
Bergen, Norway
Centrum Onkologii- Instytut; im. M.Skłodowskiej-Curie
🇵🇱
Warszawa, Poland
The Norvegian Radium Hospital Montebello; Dept of Oncology
🇳🇴
Oslo, Norway
Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii
🇵🇱
Krakow, Poland
ZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii;Wojska Polskiego 37
🇵🇱
Olsztyn, Poland
NZOZ Med.-Polonia sp. z o.o.
🇵🇱
Poznań, Poland
IPO de Lisboa; Servico de Oncologia Medica
🇵🇹
Lisboa, Portugal
IPO do Porto; Servico de Oncologia Medica
🇵🇹
Porto, Portugal
Institut of Oncology Al. Trestioreanu Bucharest; Oncology
🇷🇴
Bucuresti, Romania
Medisprof SRL
🇷🇴
Cluj-Napoca, Romania
S.C. Life Search S.R.L; Medical Oncology Clinic
🇷🇴
Timisoara, Romania
Regional Clinical Oncology Dispensary
🇷🇺
Krasnodar, Russian Federation
Russian Cancer Research Center
🇷🇺
Moscow, Russian Federation
St. Petersburg Oncology & Gynecology; City Clinical Oncology Dispensary
🇷🇺
Saint-Petersburg, Russian Federation
Moscow city oncology hospital #62 of Moscow Healthcare Department
🇷🇺
Moscow, Russian Federation
Stavropol Clinical Oncology Dispansary
🇷🇺
Stavropol, Russian Federation
Bashkirian Republican Clinical Oncology Dispensary
🇷🇺
UFA, Russian Federation
Institute for Oncology and Radiology of Serbia; Medical Oncology
🇷🇸
Belgrade, Serbia
Clinical Center Bezanijska Kosa; Oncology
🇷🇸
Belgrade, Serbia
Onkologicky ustav sv. Alzbety; Oddelenie ambulantnej chemoterapie
🇸🇰
Bratislava, Slovakia
Narodny Onkologicky Ustav; Oddelenie klinickej onkologie E
🇸🇰
Bratislava, Slovakia
Institute of Oncology Ljubljana
🇸🇮
Ljubljana, Slovenia
Universitas Annex, University of the Free State; Clinical Oncology
🇿🇦
Bloemfontein, South Africa
Cape Town Oncology Trials
🇿🇦
Cape Town, South Africa
Medical Oncology Centre of Rosebank; Oncology
🇿🇦
Johannesburg, South Africa
Cancercare
🇿🇦
Cape Town, South Africa
Steve Biko Academic Hospital; Oncology
🇿🇦
Pretoria, South Africa
Sandton Oncology Centre
🇿🇦
Sandton, South Africa
Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
🇪🇸
Santander, Cantabria, Spain
Hospital Universitario Son Espases
🇪🇸
Palma De Mallorca, Islas Baleares, Spain
Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia
🇪🇸
Las Palmas de Gran Canaria, Las Palmas, Spain
Hospital Universitario de Santa Lucía; Servicio de Oncología Médica
🇪🇸
Cartagena (Murcia), Murcia, Spain
Clinica Universitaria de Navarra; Servicio de Oncologia
🇪🇸
Pamplona, Navarra, Spain
Hospital Xeral Cíes; Servicio de Oncologia
🇪🇸
Vigo, Pontevedra, Spain
Hospital Universitario de Canarias (HUC)
🇪🇸
La Laguna (Tenerife), Tenerife, Spain
Hospital de Cruces; Servicio de Oncologia
🇪🇸
Barakaldo, Vizcaya, Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
🇪🇸
Barcelona, Spain
Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
🇪🇸
Barcelona, Spain
Hospital Clínic i Provincial; Servicio de Hematología y Oncología
🇪🇸
Barcelona, Spain
Hospital Reina Sofia
🇪🇸
Cordoba, Spain
Hospital Universitario Virgen de las Nieves; Servicio de Oncologia
🇪🇸
Granada, Spain
Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
🇪🇸
La Coruña, Spain
Complejo Asistencial Universitario de Leon; Servicio de Oncologia
🇪🇸
Leon, Spain
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸
Madrid, Spain
Hospital Universitario Clínico San Carlos; Servicio de Oncologia
🇪🇸
Madrid, Spain
Hospital Universitario 12 de Octubre; Servicio de Oncologia
🇪🇸
Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
🇪🇸
Malaga, Spain
Hospital Universitario La Paz; Servicio de Oncologia
🇪🇸
Madrid, Spain
Hospital Clinico Universitario de Salamanca; Servicio de Oncologia
🇪🇸
Salamanca, Spain
Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
🇪🇸
Malaga, Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸
Sevilla, Spain
Hospital General Universitario de Valencia; Servicio de oncologia
🇪🇸
Valencia, Spain
Instituto Valenciano Oncologia; Oncologia Medica
🇪🇸
Valencia, Spain
Hospital Universitario Miguel Servet; Servicio Oncologia
🇪🇸
Zaragoza, Spain
Sahlgrenska Universitetssjukhuset; Onkology
🇸🇪
Gothenburg, Sweden
Skånes Onkologiska Klinik, Universitetssjukhuset
🇸🇪
Lund, Sweden
Karolinska Universitetssjukhuset, Solna
🇸🇪
Stockholm, Sweden
Norrlands universitetssjukhus; Onkologkliniken
🇸🇪
Umeå, Sweden
Akademiska sjukhuset, Onkologkliniken
🇸🇪
Uppsala, Sweden
Universitaetsspital Basel; Onkologie
🇨🇭
Basel, Switzerland
Inselspital Bern; Medizinische Onkologie
🇨🇭
Bern, Switzerland
Kantonsspital Graubünden;Onkologie und Hämatologie
🇨🇭
Chur, Switzerland
CHUV; Departement d'Oncologie
🇨🇭
Lausanne, Switzerland
Kantonsspital St. Gallen; Onkologie/Hämatologie
🇨🇭
St. Gallen, Switzerland
Universitätsspital Zürich; Dermatologische Klinik
🇨🇭
Zürich, Switzerland
Adana Baskent University Hospital; Medical Oncology
🇹🇷
Adana, Turkey
Ankara Uni , Ibn-I Sina Hospital; Oncology Dept
🇹🇷
Ankara, Turkey
Akdeniz University School of Medicine; General Surgery
🇹🇷
Antalya, Turkey
Cukurova Uni Faculty of Medicine; Medical Oncology
🇹🇷
Adana, Turkey
Gazi Uni Medical Faculty Hospital; Oncology Dept
🇹🇷
Ankara, Turkey
Dokuz Eylul Uni ; Medical Oncology
🇹🇷
Izmir, Turkey
Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology
🇹🇷
Istanbul, Turkey
American Hospital, Medical Oncology Department
🇹🇷
Istanbul, Turkey
Gaziantep University Medical Faculty, Medical Oncology Department
🇹🇷
Gaziantep, Turkey
Kartal Training and Research Hospital;Medical Oncology Department
🇹🇷
Istanbul, Turkey
Ege University Medical Faculty; Medical Oncology Department
🇹🇷
Bornova, İZMİR, Turkey
Hacettepe Uni Medical Faculty Hospital; Oncology Dept
🇹🇷
Sıhhiye, ANKARA, Turkey
Addenbrookes Nhs Trust; Oncology Clinical Trials Unit
🇬🇧
Cambridge, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧
Glasgow, United Kingdom
Royal Surrey County Hospital; St. Lukes Cancer Centre
🇬🇧
Guildford, United Kingdom
St James University Hospital
🇬🇧
Leeds, United Kingdom
Churchill Hospital; Oxford Cancer and Haematology Centre
🇬🇧
Oxford, United Kingdom
Royal Marsden Hospital
🇬🇧
London, United Kingdom
Christie Hospital; Breast Cancer Research Office
🇬🇧
Manchester, United Kingdom
Northern Centre for Cancer Care Freeman Hospital; Sir Bobby Robson Cancer Trials Research Centre
🇬🇧
Newcastle upon Tyne, United Kingdom
Mount Vernon Hospital; Centre For Cancer Treatment
🇬🇧
Northwood, United Kingdom
Southampton General Hospital; Medical Oncology
🇬🇧
Southampton, United Kingdom
Singleton Hospital; Oncology
🇬🇧
Swansea, United Kingdom
POKO Poprad; Department of Oncology
🇸🇰
Poprad, Slovakia
Alfred Hospital
🇦🇺
Melbourne, Victoria, Australia
Medizinische Universität Wien; Univ.Klinik für Dermatologie
🇦🇹
Wien, Austria
Rigas Austrumu Kliniska Universitates slimnica, Latvijas Onkologijas centrs
🇱🇻
Riga, Latvia
St. Boniface General Hospital; Medicine
🇨🇦
Winnipeg, Manitoba, Canada
Sir Charles Gairdner Hospital
🇦🇺
Nedlands, Western Australia, Australia
Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology
🇮🇳
New Delhi, Delhi, India
Azienda Ospedaliera S. Maria - Terni; Oncologia
🇮🇹
Terni, Umbria, Italy
Ranbam Health Care Campus; Oncology - Hafia
🇮🇱
Hafia, Israel
A.O. Universitaria Policlinico Di Modena; Oncologia
🇮🇹
Modena, Emilia-Romagna, Italy
Policlinico Le Molinette; Clinica Dermatologica
🇮🇹
Torino, Piemonte, Italy
A.O.U. Senese Policlinico Santa Maria Alle Scotte
🇮🇹
Siena, Toscana, Italy
AO Santa Maria Nuova; U.O. Day Hospital di Oncologi
🇮🇹
Reggio Emilia, Emilia-Romagna, Italy
A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia
🇮🇹
Udine, Friuli-Venezia Giulia, Italy
Asst Papa Giovanni XXIII; Oncologia Medica
🇮🇹
Bergamo, Lombardia, Italy
Az. Osp. Spedali Civili; Divisione Di Oncologia - Iii Medicina
🇮🇹
Brescia, Lombardia, Italy
Policlinico P. Giaccone; Istituto Di Oncologia, Clinica Medica 1
🇮🇹
Palermo, Sicilia, Italy
Irccs Ospedale San Raffaele;Oncologia Medica
🇮🇹
Milano, Lombardia, Italy
Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
🇮🇹
Milano, Lombardia, Italy
Istituto Tumori Giovanni Paolo II IRCSS; Ospedale Oncologico Bari
🇮🇹
Bari, Puglia, Italy
Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
🇮🇹
Firenze, Toscana, Italy
Azienda Ospedaliera S. Chiara; Dip di Onc,Trapianti e delle Nuove Tecnologie in Medicina
🇮🇹
Pisa, Toscana, Italy
Melanoma Institute Australia
🇦🇺
North Sydney, New South Wales, Australia
Royal Adelaide Hospital; Oncology
🇦🇺
Adelaide, South Australia, Australia
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
🇨🇦
Toronto, Ontario, Canada
Tata Memorial Hospital; Dept of Medical Oncology
🇮🇳
Mumbai, Maharashtra, India
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹
Napoli, Campania, Italy
Hospital Univ. Central de Asturias; Servicio de Oncologia
🇪🇸
Oviedo, Asturias, Spain
Nottingham University Hospitals City Campus
🇬🇧
Nottingham, United Kingdom
Universitätsklinikum Schleswig-Holstein; Campus Lübeck
🇩🇪
Lübeck, Germany
Inst. Alexander Fleming; Oncologia
🇦🇷
Buenos Aires, Argentina
Hospital Hygeia; 1St Oncology Dept.
🇬🇷
Athens, Greece
East Tallinn Central Hospital; Clinic of Internal Medicine
🇪🇪
Tallinn, Estonia
Univ General Hosp Heraklion; Medical Oncology
🇬🇷
Heraklion, Greece
Semmelweis Egyetem; Bor-, Nemikortani es Boronkologiai Klinika
🇭🇺
Budapest, Hungary
FSBI "Scientific Research Institute of Oncology named after N.N.Petrov" Ministry of Health of RF
🇷🇺
St Petersburg, Leningrad, Russian Federation
Hospital Sao Jose
🇧🇷
São Paulo, SP, Brazil