Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma
- Conditions
- Metastatic or Unresectable Cutaneous Melanoma
- Interventions
- Registration Number
- NCT01763164
- Lead Sponsor
- Pfizer
- Brief Summary
Two-arm, randomized, prospective, open-label, multi-center, phase III study to compare the efficacy and safety of MEK162 (45 mg BID) versus dacarbazine (1000 mg/m2 IV every 3 weeks) in patients with advanced (Stage IIIC) unresectable or metastatic (Stage IV) NRAS Q61 mutation-positive cutaneous or unknown primary melanoma. The mutation analysis will be performed at a central laboratory. Only those patients with Q61 mutation per central laboratory and meet all eligibility criteria will be randomized. A total of 393 patients will be randomized 2:1 to receive either MEK162 or dacarbazine. Patients will be stratified according to AJCC stage (IIIC, IVM1a, and IVM1b versus IVM1c), ECOG Performance status (0 versus 1) and any prior number of lines of immunotherapy (immunotherapies versus none). This study will use an Interactive Response Technology (IRT). The primary end point of the study is progression-free survival. Key secondary end point is overall survival
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 402
- Diagnosis of locally advanced, unresectable or metastatic cutaneous or melanoma of unknown primary AJCC Stage IIIC or IV (uveal and mucosal melanoma are excluded)
- Presence of NRAS Q61 mutation in tumor tissue prior to randomization as determined by a Novartis designated central laboratory
- Naïve untreated patients or patients who have progressed on or after any number of prior lines of immunotherapy for unresectable locally advanced or metastatic melanoma
- Evidence of at least one measurable lesion as detected by radiological or photographic methods
- Adequate bone marrow, organ function, cardiac and laboratory parameters
- Normal functioning of daily living activities
- Any untreated CNS metastases
- Uveal or mucosal melanoma
- History of or current evidence of retinal vein occlusion (RVO) or risk factors of RVO
- Patients with washout period < 6 weeks from the last dose of ipilimumab or other immunotherapy.
- Previous systemic chemotherapy for unresectable locally advanced or metastatic melanoma.
- History of Gilbert's syndrome
- Prior therapy with a MEK- inhibitor
- Impaired cardiovascular function or clinically significant cardiovascular diseases
- Uncontrolled arterial hypertension despite medical treatment
- HIV positive or active Hepatitis A or B
- Impairment of gastrointestinal function
- Patients who have undergone major surgery or radiotherapy ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure;
- Patients with neuromuscular disorders that are associated with elevated CK.
- Pregnant or nursing (lactating) women
- Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study
Other protocol-defined inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MEK162 MEK162 - Dacarbazine Dacarbazine -
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 From the date of randomization to the date of the first documented PD or death, whichever occurred first (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm) PFS: time from randomization to first documented PD or death due to any cause, whichever occurred first. RECIST 1.1, PD: \>=20% increase in sum of diameter of target lesions (TLs) taking as reference the smallest sum on study (including baseline sum), sum must also be an absolute increase of \>=5 mm; unequivocal progression of existing non-TLs; appearance of \>=1 lesion. Complete response (CR): disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to \<10 mm; normalization of tumor marker level for non-TLs. Partial response (PR): \>=30% decrease in sum of diameter of all TLs, referring baseline sum of diameters. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor increase in lesions qualified for PD referring smallest sum diameter. With no event at time of analysis cut-off or at start of any new anti-neoplastic therapy, PFS censored at date of last adequate tumor assessment of CR, PR or SD.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From the date of randomization to the date of death (maximum up to 107 weeks for binimetinib arm; maximum up to 88 weeks for dacarbazine arm) Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a participant was not known to have died, overall survival was censored at the date of last known date participant alive.
Duration of Objective Response (DOR) From the date of first documented response (CR or PR) to the first documented progression or death (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm) DOR: time from date of first documented response (CR or PR) to first documented progression or death due to underlying cancer. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to \<10 mm; normalization of tumor marker level for non-TLs; b) PR: \>=30% decrease in sum of diameter (dia) of all TLs, referring baseline sum of dia; c) PD: \>=20% increase in sum of diameter of all measured target lesions taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of \>=5 mm. Unequivocal progression of existing non-target lesions. Appearance of at least 1 new lesion. If a participant with a CR or PR had no PD or death due to underlying cancer, participants was censored at date of last adequate tumor assessment.
Number of Participants With Clinically Notable Vital Signs From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm Abnormalities criteria included: low/high pulse rate (beats per minute \[bpm\]):\<=50bpm with decrease from baseline \>=15bpm/\>=120bpm with increase from baseline \>=15bpm; Low/high systolic blood pressure (millimeters of mercury \[mmHg\]): \<=90mmHg with decrease from baseline \>=20mmHg/\>=160mmHg with increase from baseline \>=20mmHg; Low/high diastolic blood pressure \[mmHg\]: \<=50mmHg with decrease from baseline \>=15mmHg/\>=100mmHg with increase from baseline \>=15mmHg; Low/high body weight (kilogram \[kg\]): \>=20% decrease from baseline / \>=10% increase from baseline; Low/high body temperature (degree Celsius \[°C\]): \<=36°C / \>= 37.5°C
Overall Response Rate (ORR) From date of randomization until first documented response of CR or PR (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm) ORR: percentage of participants with best overall response (BOR) of CR or PR. BOR: best response recorded from start of treatment until CR or PR. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to \<10 mm; normalization of tumor marker level for non-TLs; b) PR: \>=30% decrease in sum of diameter of all TLs, taking as reference baseline sum of diameters. ORR is reported for confirmed and unconfirmed responses. Confirmed CR or PR = at least 2 determinations of CR or PR at least 4 weeks apart before PD. PD: \>=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of \>=5 mm. Unequivocal progression of existing non TLs. Appearance of at least 1 new lesion.
Disease Control Rate (DCR) From date of randomization until first documented response of CR, PR, SD or non-CR/non-PD (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm) DCR was calculated as the percentage of participants with a BOR of CR, PR, SD RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to \<10 mm; normalization of tumor marker level for non-TLs; b) PR: \>=30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; c) SD: neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD taking as reference the smallest sum diameters; d) PD: \>=20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of \>=5 mm. Unequivocal progression of existing non-target lesions. Appearance of at least 1 new lesion.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) From baseline up to 219.4 weeks for binimetinib arm; From baseline up to 123.9 weeks for dacarbazine arm An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period. AEs included all SAEs and non-SAEs.
Time to Response (TTR) From date of randomization until first documented response of CR or PR (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm) TTR: time between date of randomization until first documented response of CR or PR. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to \<10 mm; normalization of tumor marker level for non-TLs; b) PR: \>=30% decrease in sum of diameter (dia) of all TLs, referring baseline sum of dia; c) PD: \>=20% increase in sum of diameter of all measured TLs taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of \>=5 mm. Unequivocal progression of existing non-TLs. Appearance of \>=1 new lesion. Participants who did not achieve PR or CR censored at last adequate tumor assessment date when they did not have PFS event (time from date of randomization to date of first documented PD or death due to any cause, whichever occur first) or at maximum follow-up when they had PFS event.
Number of Participants With Clinically Notable Hematology Shifts Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03 From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm Clinically notable shifts are defined as worsening by at least 2 grades or to \>= grade 3. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.
Number of Participants With Notable Electrocardiogram (ECG) Values From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm Criteria for notable ECG values were as follow: QT interval (in millisecond \[msec\]) new (newly occurring post-baseline value) greater than (\>) 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Fredericia formula (QTcF) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Bazett's formula (QTcB) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; heart rate in bpm new (newly occurring post-baseline value) \<60 and \>100.
Number of Participants With Adverse Events of Special Interest: Cardiac Events From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Here, in this outcome measure data is reported for events falling in any of the grades.
Number of Participants With Clinically Significant Findings in Physical Examination From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm A complete physical examination included the examination of general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and neurological systems. If indicated based on medical history and/or symptoms, rectal, external genitalia, breast, and pelvic examinations were performed. Clinical significance in physical examination was reported as adverse events.
Number of Participants With Clinically Notable Clinical Chemistry/Biochemistry Shifts Based on NCI-CTCAE Grade, Version 4.03 From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm Clinically notable shifts are defined as worsening by at least 2 grades or to \>= grade 3. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.
Number of Participants With Adverse Events of Special Interest: Ocular Events From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Grade 1: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL; Grade 3: Severe or medically significant but not immediately sight threatening; Hospitalization or prolongation of existing hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Sight-threatening consequences; urgent intervention indicated; blindness (20/200 or worse) in the affected eye. Here, in this outcome measure data is reported for events falling in any of the grades.
Plasma Concentration of Binimetinib Day 1 of Week 1: Pre-dose, 1, 1.5, 2, 10 hours post-dose; Day 1 of Weeks 4, 7: Pre-dose, 1.5 hours post-dose; Day 1 of Weeks 10, 13: Pre-dose Time to Definitive 10% Deterioration in Global Health Status Score of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm The time to definitive 10% deterioration was defined as the time from the date of randomization to the date of event, which was defined as death due to any cause or at least 10% worsening of the corresponding scale score, relative to baseline, with no later improvement above this threshold observed during the course of the study or death due to any cause. If a participant had no event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last adequate health related quality of life (HRQoL) evaluation. EORTC QLQ-C30: 5 functional scales (physical, role, cognitive, emotional, and social), a global health status scale, 3 symptom scales (nausea/vomiting, pain, fatigue) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All scales and single-item measures range =0 to 100. High score for global health status = high quality of life.
Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Weeks 4, 7, 13, 19, 25, 34, 43, 52, 61, 70, End of Treatment, Safety Follow-up Visit, Post-Treatment Follow-up Visit 1, 2, 3, 4, 5 and 6 Both arms: Baseline, Day 1 Treatment Week (TW) 4,7,13,19,25,34,43,52; Post-treatment follow-up Visit (FUV) 1 to 6; Binimetinib: Day 1 TW61,70; End of treatment (EOT= TW73); Safety FUV=30 days post TW73; Dacarbazine: EOT=TW 57;Safety FUV=30 days post TW57 EORTC QLQ-C30: 5 functional scales (physical, role, cognitive, emotional, and social), a h global health status scale, 3 symptom scales (nausea/vomiting, pain, fatigue) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All scales and single-item measures range =0 to 100. High score for global health status = high quality of life. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.
Change From Baseline in EuroQoL-5 Dimensions- 5 Levels (EQ-5D-5L) Index Score at Weeks 4, 7, 13, 19, 25, 34, 43, 52, 61, 70, End of Treatment, Safety Follow-up Visit, Post-treatment Follow-up Visit 1, 2, 3, 4, 5 and 6 Both arms: Baseline, Day 1 Treatment Week (TW) 4,7,13,19,25,34,43,52; Post-treatment follow-up Visit (FUV) 1 to 6; Binimetinib: Day 1 TW61,70; End of treatment (EOT= TW73); Safety FUV=30 days post TW73; Dacarbazine: EOT=TW 57;Safety FUV=30 days post TW57 EQ-5D-5L, is a standardized measure of health utility that provides a single index value for one's health status. EQ-5D-5L contained 1 item for each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Index score: participant responses to the 5 dimensions reflected a specific health state that corresponded to a population preference weight for that state on a continuous scale of 0 (death) to 1 (perfect health). Higher index scores = better health state. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.
Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) From baseline up to 73 weeks 3 days for binimetinib arm; From baseline up to 57 weeks 3 days for dacarbazine arm ECOG PS was used to assess the physical health of participants, and ranged from 0 (most active) to 5 (dead). ECOG PS grades: 0= fully active, able to carry on all pre-disease performance without restriction, 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 2= ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours, 3= capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4=completely disabled. cannot carry on any selfcare. Totally confined to bed or chair and 5= dead. Definitive deterioration is defined as on treatment death due to any cause or decrease in ECOG PS by at least one category from baseline score.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) For both arms: Baseline, Weeks 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55 and 30-day Follow-up For binimetinib only: Weeks 58, 61, 64, 67, 70, 73 ECOG PS was used to assess the physical health of participants, and ranged from 0 (most active) to 5 (dead). ECOG PS grades: 0= fully active, able to carry on all pre-disease performance without restriction, 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 2= ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours, 3= capable of only limited self-care, 4=completely disabled. cannot carry on any selfcare. Totally confined to bed or chair confined to bed or chair more than 50% of waking hours and 5= dead. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.
Number of Participants With Neuroblastoma RAS Viral (V-ras) Oncogene Homolog (NRAS) Mutation Status at Baseline Baseline Number of participants with NRAS mutation status at baseline were reported.
Trial Locations
- Locations (191)
Harry and Jeannette Weinberg Cancer Institute @Franklin Square
🇺🇸Baltimore, Maryland, United States
The Ohio State University James Cancer Hospital
🇺🇸Columbus, Ohio, United States
St. Luke's Hospital - Allentown Campus
🇺🇸Allentown, Pennsylvania, United States
UT Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
UT Southwestern University Hospital - Zale Lipshy
🇺🇸Dallas, Texas, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Noord-holland, Netherlands
Leids Universitair Medisch Centrum
🇳🇱Leiden, Zuid-holland, Netherlands
Hospital de Clinicas de Passo Fundo
🇧🇷Passo Fundo, RIO Grande DO SUL, Brazil
CHU Angers
🇫🇷Angers, Maine-et-loire, France
Broomfield Hospital
🇬🇧Chelmsford, Essex, United Kingdom
Charite Campus Mitte
🇩🇪Berlin, Schleswig-holstein, Germany
Hospital Moinhos de Vento
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Ege University Medical Faculty
🇹🇷Bornova, Izmir, Turkey
Salzburger Landeskliniken
🇦🇹Salzburg, Austria
Allgemeines Krankenhaus der Stadt Wien
🇦🇹Vienna, Austria
Centrum Medyczne MAVIT Sp. z o.o.
🇵🇱Warszawa, Mazowieckie, Poland
Universitätsspital Zürich
🇨🇭Zurich, Zürich (DE), Switzerland
Magyar Honvédség Egészségügyi Központ
🇭🇺Budapest, Hungary
Centro de Investigación Clínica ? Clínica Viedma
🇦🇷Viedma, RÍO Negro, Argentina
Centro Oncologico de Rosario
🇦🇷Rosario, Santa FE, Argentina
Universitätsklinikum Innsbruck
🇦🇹Innsbruck, Tirol, Austria
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
🇵🇹Lisbon, Lisboa, Portugal
Klinikum Mannheim Universitätsklinikum gGmbH
🇩🇪Mannheim, Baden-württemberg, Germany
LKH-Universitätsklinikum Klinikum Graz
🇦🇹Graz, Steiermark, Austria
Hospital Regional Universitario de Malaga Hospital General
🇪🇸Malaga, Málaga, Spain
Istituto Dermopatico dell'Immacolata IRCCS
🇮🇹Roma, Lazio, Italy
Radboud University Nijmegen Medical Centre
🇳🇱Nijmegen, Gelderland, Netherlands
Royal Preston Hospital
🇬🇧Preston, Lancashire, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, Cornwall, United Kingdom
Klinikum Nuernberg Nord
🇩🇪Nürnberg, Germany
Universitaetsklinikum Freiburg
🇩🇪Freiburg im Breisgau, Baden-württemberg, Germany
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
🇭🇺Szolnok, Hungary
Laiko General Hospital of Athens
🇬🇷Athens, Greece
Centre Hospitalier Universitaire Hopitaux de Rouen
🇫🇷Rouen, France
Universitatsklinikum Leipzig
🇩🇪Leipzig, Sachsen, Germany
Hôpital Robert Debré
🇫🇷Reims, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
CHRU de Lille - Hôpital Huriet
🇫🇷Lille, Nord, France
AOU dell'Università degli Studi della Campania Luigi Vanvitelli
🇮🇹Napoli, Campania, Italy
Istituto Oncologico Veneto - I.R.C.C.S.
🇮🇹Padova, Veneto, Italy
Hôpital Saint Louis
🇫🇷Paris, France
Shinshu University Hospital
🇯🇵Matsumoto, Nagano, Japan
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Vseobecna Fakultni Nemocnice V Praze
🇨🇿Praha 2, Czechia
CHU de Quebec - L'Hotel-Dieu de Quebec
🇨🇦Quebec, Canada
Centre Hospitalier Universitaire Ambroise Pare
🇫🇷Boulogne Billancourt, France
Elben Klinken Stade Buxtehude
🇩🇪Buxtehude, Niedersachsen, Germany
Institut für Diagnostische und Interventionelle Radiologie Frankfurt
🇩🇪Frankfurt, Hessen, Germany
Centre Hospitalier Le Mans
🇫🇷Le Mans, France
Groupe Hospitalier Archet I Et II
🇫🇷Nice, France
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
🇫🇷Lyon, Rhône, France
Somogy Megyei Kaposi Mór Oktató Kórház
🇭🇺Kaposvár, Hungary
Universitätsklinikum Frankfurt
🇩🇪Frankfurt, Hessen, Germany
Hôpital Saint-André
🇫🇷Bordeaux, France
Johannes Wesling Klinikum Minden
🇩🇪Minden, Nordrhein-westfalen, Germany
Helios Klinikum Erfurt
🇩🇪Erfurt, Thüringen, Germany
Universitätsklinikum Carl Gustav Carus an der TU Dresden
🇩🇪Dresden, Germany
University Clinic Heidelberg - PPDS
🇩🇪Heidelberg, Germany
Fachklinik Hornheide
🇩🇪Münster, Germany
Severance Hospital Yonsei University Health System - PPDS
🇰🇷Seoul, Korea, Republic of
Rambam Medical Center - PPDS
🇮🇱Haifa, Israel
Sheba Medical Center - PPDS
🇮🇱Ramat Gan, Israel
National Cancer Center Hospital
🇯🇵Chuo-ku, Japan
Universit*ätsklinikum Ulm
🇩🇪Ulm, Germany
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
🇮🇹Brescia, Lombardia, Italy
Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie
🇵🇱Warszawa, Poland
Narodny onkologicky ustav
🇸🇰Bratislava, Slovakia
Sandton Oncology Medical Research
🇿🇦Johannesburg, Gauteng, South Africa
Azienza Ospedaliera Universitaria Senese
🇮🇹Siena, Italy
Hadassah Medical Center - PPDS
🇮🇱Jerusalem, Israel
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebrón - PPDS
🇪🇸Barcelona, Spain
Kansai Medical University Hospital
🇯🇵Hirakata-city, Japan
Asan Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale
🇮🇹Napoli, Naples, Italy
Lux Med
🇵🇱Warszawa, Poland
Hospital Garcia de Orta*E.P.E.
🇵🇹Almada, Portugal
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
🇵🇹Porto, Portugal
Isala Klinieken
🇳🇱Zwolle, Netherlands
University of The Free State
🇿🇦Bloemfontein, FREE State, South Africa
Sandton Oncology Medical Group
🇿🇦Johannesburg, Gauteng, South Africa
Mary Potter Oncology Centre
🇿🇦Pretoria, Gauteng, South Africa
Clinica Universidad Navarra
🇪🇸Pamplona, Navarra, Spain
Russian Oncology Research Center n a N N Blokhin
🇷🇺Moscow, Russian Federation
St James s Institute of Clinical Oncology
🇬🇧Leeds, United Kingdom
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Fundacion Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Adana Ba?kent Hastanesi K??la Yerle?kesi
🇹🇷Adana, Turkey
Royal Marsden Hospital - Surrey
🇬🇧London, London, CITY OF, United Kingdom
Skanes Universitetssjukhus Lund
🇸🇪Lund, Sweden
The Royal Sussex County Hospital
🇬🇧Brighton, EAST Sussex, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Kresge Eye Institute
🇺🇸Detroit, Michigan, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
OHSU Knight Cancer Institute
🇺🇸Portland, Oregon, United States
Kaiser Permanente Northwest Region Oncology/Hematology
🇺🇸Portland, Oregon, United States
OHSU Center for Health and Healing
🇺🇸Portland, Oregon, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
IRCCS Giovanni Paolo II Istituto Oncologico
🇮🇹Bari, Italy
ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Fondazione IRCCS 'Istituto Nazionale dei Tumori' di Milano
🇮🇹Milano, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Italy
A.O.U. Città della Salute e della Scienza di Torino - Presidio S. Lazzaro
🇮🇹Torino, Italy
Hopitaux de La Timone
🇫🇷Marseille, France
Clatterbridge Hospital
🇬🇧Wirral, United Kingdom
MD Anderson Cancer Center
🇪🇸Madrid, Spain
Consorcio Hospital General Universitario de Valencia
🇪🇸Valencia, Spain
Klinikum Dorothea Christiane Erxleben Quedlinburg GmbH
🇩🇪Quedlinburg, Sachsen-anhalt, Germany
Uniklinik Köln
🇩🇪Koeln, Germany
Medizinische Hochschule Hannover (Hannover Medical School)
🇩🇪Hannover, Germany
Universitatsklinikum Schleswig-Holstein
🇩🇪Lübeck, Germany
Lake Macquarie Private Hospital
🇦🇺Gateshead, New South Wales, Australia
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Cooper University Hospital
🇺🇸Voorhees, New Jersey, United States
The Ohio State University Martha Morehouse Medical Plaza
🇺🇸Columbus, Ohio, United States
Florida Cancer Specialists
🇺🇸Venice, Florida, United States
SRH Wald-Klinikum Gera GmbH
🇩🇪Gera, Germany
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Melanoma Institute Australia
🇦🇺North Sydney, New South Wales, Australia
Universitätsklinikum Würzburg
🇩🇪Würzburg, Bayern, Germany
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Singleton Hospital - PPDS
🇬🇧Swansea, Glamorgan, United Kingdom
Highlands Oncology Group
🇺🇸Rogers, Arkansas, United States
Oncology Specialists, SC
🇺🇸Park Ridge, Illinois, United States
Goshen Center For Cancer Care
🇺🇸Goshen, Indiana, United States
Karmanos Cancer Institute of Farmington Hills
🇺🇸Farmington Hills, Michigan, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
OHSU
🇺🇸Portland, Oregon, United States
Cancer Center Associates - Medical Oncology
🇺🇸Bethlehem, Pennsylvania, United States
St. Luke's Cancer Center - Allentown Campus
🇺🇸Allentown, Pennsylvania, United States
St. Luke's University Hospital - Bethlehem Campus
🇺🇸Bethlehem, Pennsylvania, United States
St. Luke's Cancer Center - Anderson Campus
🇺🇸Easton, Pennsylvania, United States
Thomas Jefferson Medical Oncology
🇺🇸Philadelphia, Pennsylvania, United States
St. Luke's Hospital - Quakertown Campus
🇺🇸Quakertown, Pennsylvania, United States
Hospital of the University of Pennsylvania, Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Texas Oncology-Austin Central
🇺🇸Austin, Texas, United States
Elliot J. Ginchansky, MD, PA
🇺🇸Dallas, Texas, United States
Dennis B. Kay
🇺🇸Dallas, Texas, United States
UT Southwestern University Hospital- St. Paul
🇺🇸Dallas, Texas, United States
Parkland Memorial Hospital
🇺🇸Dallas, Texas, United States
Texas Oncology-Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
US Oncology
🇺🇸The Woodlands, Texas, United States
Sanatorio de La Providencia
🇦🇷Buenos Aires, Ciudad Autónoma DE Buenosaires, Argentina
Fundacion CIDEA
🇦🇷Buenos Aires, Argentina
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Chris O'Brien Lifehouse Hospital
🇦🇺Camperdown, New South Wales, Australia
Sint-Augustinuskliniek
🇧🇪Wilrijk, Antwerpen, Belgium
CHU Sart Tilman
🇧🇪Liege, Belgium
INCA Instituto Nacional de Cancer
🇧🇷Rio de Janeiro, Brazil
Hospital São José
🇧🇷Sao Paulo, Brazil
Alberta Health Services - Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Sunnybrook Research Institute Centre
🇨🇦Toronto, Ontario, Canada
McGill University Health Center / Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
Mou/Mmci - Ppds
🇨🇿Brno, Jihomoravský KRAJ, Czechia
LMU Klinikum der Universität München
🇩🇪München, Bayern, Germany
Service de PneumologieCHU Lyon Sud
🇫🇷Pierre Benite, France
University Clinic Regensburg - PPDS
🇩🇪Regensburg, Bayern, Germany
IRCCS Az. Osp. Universitaria San Martino- IST
🇮🇹Genova, Italy
Ospedale San Raffaele S.r.l. - PPDS
🇮🇹Milano, Italy
Samsung Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Ryazan Regional Clinical Oncology Dispensary
🇷🇺Ryazan, Russian Federation
Scientific Research Institute of Oncology n.a. N.N. Petrov
🇷🇺St. Petersburg, Russian Federation
Steve Biko Academic Hospital
🇿🇦Pretoria, Gauteng, South Africa
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario HM Sanchinarro - CIOCC
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario Insular - Materno Infantil
🇪🇸Gran Canaria, Spain
Hospital Universitario A Coruña
🇪🇸La Coruna, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Virgen de La Salud
🇪🇸Toledo, Spain
Hôpitaux Universitaires de Genève
🇨🇭Genève, Switzerland
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Baskent University Medical Faculty Ankara Hospital
🇹🇷Ankara, Turkey
Istanbul University Cerrahpasa Medical Faculty Hospital
🇹🇷Istanbul, Turkey
Bristol Haematology and Oncology Centre
🇬🇧Bristol, Bristol, CITY OF, United Kingdom
UZ Gasthuisberg
🇧🇪Leuven, Belgium
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States