Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib as First-line Therapy in Participants With Advanced Hepatocellular Carcinoma (MK-7902-002/E7080-G000-311/LEAP-002)
- Conditions
- Carcinoma, Hepatocellular
- Interventions
- Registration Number
- NCT03713593
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of lenvatinib (E7080/MK-7902) in combination with pembrolizumab (MK-3745) versus lenvatinib in combination with placebo as first-line therapy for the treatment of advanced hepatocellular carcinoma in adult participants.
The primary hypotheses of this study are that lenvatinib plus pembrolizumab is superior to lenvatinib plus placebo with respect to progression-free survival (PFS) and overall survival (OS).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 794
- Is male or female and ≥18 years of age at the time of signing the informed consent
- Has a diagnosis of hepatocellular carcinoma confirmed by radiology, histology, or cytology
- Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
- Has a Child-Pugh class A liver score
- Has a predicted life expectancy of >3 months
- Has at least one measurable hepatocellular carcinoma (HCC) lesion based on RECIST 1.1 as confirmed by BICR
- Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
- Participants with hepatitis B will be eligible as long as their virus is well controlled
- Has had esophageal or gastric variceal bleeding within the last 6 months
- Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
- Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula
- Has clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study intervention
- Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability
- Has had major surgery to the liver within 4 weeks prior to the first dose of study intervention
- Has had a minor surgery (ie, simple excision) within 7 days prior to the first dose of study intervention
- Has serious non-healing wound, ulcer, or bone fracture
- Has received any systemic chemotherapy for HCC or chemotherapy for any malignancy in the past 3 years
- Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, or CD137)
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that has undergone potentially curative therapy
- Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator
- Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of their excipients
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has urine protein ≥1 grams/24 hours
- Prolongation of corrected QT (QTc) interval to >480 milliseconds (corrected by Fridericia Formula)
- Has left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
- Has an active infection requiring systemic therapy with the exceptions of hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Has a known history of human immunodeficiency virus (HIV) infection
- Has known active tuberculosis (Bacillus tuberculosis)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention
- Has had an allogenic tissue/solid organ transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description lenvatinib plus placebo saline placebo Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity. lenvatinib plus pembrolizumab pembrolizumab Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity. lenvatinib plus placebo lenvatinib Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally QD plus saline placebo by IV infusion on Day 1 Q3W. Saline placebo will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity. lenvatinib plus pembrolizumab lenvatinib Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight \<60 kg) orally once a day (QD) plus pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W). Pembrolizumab will be administered for up to 35 cycles (approximately 24 months). Lenvatinib will be administered until progressive disease or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 41 months PFS was defined as the time from the date of the first documentation of disease progression, as determined by blinded independent central review (BICR) per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter \[mm\]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.
Overall Survival (OS) Up to approximately 41 months OS was defined as the time from randomization until death from any cause
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 41 months ORR was defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 41 months DOR was determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR, per RECIST 1.1 as assessed by BICR, until the first documented disease progression or death due to any cause, whichever occurred first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 41 months DCR was defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per RECIST 1.1 as assessed by BICR. SD must be achieved at ≥6 weeks after randomization to be considered best overall response. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Time to Disease Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Up to approximately 41 months TTP was defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by BICR. RECIST 1.1 was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.
Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Up to approximately 41 months PFS was defined as the time from the first dose of study intervention to the first documented progressive disease (PD) per mRECIST by BICR or death due to any cause, whichever occurred first. mRECIST for HCC allowed evaluation of treatment effects that were not reflected in simple total size changes of lesions. Per mRECIST, PD was defined as an increase of at least 20% in the sum of diameters (SODs) of viable (enhancing) target lesions, taking as reference the smallest SODs of viable (enhancing) target lesions recorded since the treatment started.
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Up to approximately 41 months ORR wass defined as the percentage of participants who have a confirmed complete response (CR: disappearance of any intratumoral arterial enhancement in all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of viable \[enhancement in the arterial phase\] target lesions, taking as reference the baseline sum of the diameters of target lesions) per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.
Duration of Response (DOR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Up to approximately 41 months DOR was determined by disease assessment and is defined as the time from the first documented evidence of a response of CR or PR, per mRECIST as assessed by BICR, until the first documented disease progression or death due to any cause, whichever occurs first. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.
Disease Control Rate (DCR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Up to approximately 41 months DCR was defined as the percentage of participants who have a best overall response of CR, PR, or SD per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. SD must be achieved at ≥6 weeks after randomization to be considered best overall response. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.
Time to Disease Progression (TTP) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Up to approximately 41 months TTP was defined as the time from randomization to the first documented disease progression per mRECIST as assessed by BICR. mRECIST for hepatocellular carcinoma evaluates lesions within the liver parenchyma showing increased contrast enhancement in the arterial phase. A maximum of 10 target lesions and a maximum of 5 target lesions per organ were followed.
Number of Participants Who Experienced an Adverse Event (AE) Up to approximately 41 months Number of participants who experienced an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment
Number of Participants Who Experienced an Serious Adverse Event (SAE) Up to approximately 41 months Number of participants who experienced a SAE defined as an AE that resulted in death, was life threatening, resulting in persistent or significant disability or incapacity, resulting in or prolonged a hospitalization, was a congenital anomaly or birth defect, was a cancer, was associated with an overdose, or was another important medical event
Number of Participants Who Experienced an Immune-related Adverse Event (irAE) of Clinical Interest Up to approximately 41 months Number of participants who experienced an AE representing an immunologic etiology and considered to be causally related to drug exposure
Number of Participants Who Experienced an Hepatic Event of Clinical Interest (HECI) Up to approximately 41 months Number of participants who experienced a hepatic ECI not due to disease progression as judged by the investigator.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event Up to approximately 41 months Number of participants who discontinued study treatment due to an AE
Trial Locations
- Locations (172)
Emory University Winship Cancer Institute ( Site 0639)
🇺🇸Atlanta, Georgia, United States
Beth Israel Deaconess Medical Center ( Site 0716)
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital ( Site 0603)
🇺🇸Boston, Massachusetts, United States
Princess Alexandra Hospital ( Site 0007)
🇦🇺Wooloongabba, Queensland, Australia
Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 0419)
🇵🇱Bytom, Slaskie, Poland
Ars Medical Sp. z o.o. ( Site 0433)
🇵🇱Pila, Poland
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0450)
🇷🇺Krasnoyarsk, Russian Federation
Hospital Universitario Ramon y Cajal ( Site 0514)
🇪🇸Madrid, Spain
Hospital Universitario La Paz ( Site 0510)
🇪🇸Madrid, Spain
Abdurrahman Yurtaslan Onkoloji Hastanesi ( Site 0551)
🇹🇷Ankara, Turkey
Inonu Universitesi Medical Fakultesi ( Site 0545)
🇹🇷Malatya, Turkey
National Taiwan University Hospital ( Site 0523)
🇨🇳Taipei, Taiwan
900 Hospital of the Joint ( Site 0091)
🇨🇳Fuzhou, Fujian, China
Guangdong General Hospital ( Site 0092)
🇨🇳Guangzhou, Guangdong, China
University of Miami, Sylvester Comprehensive Cancer Center ( Site 0596)
🇺🇸Miami, Florida, United States
Siriraj Hospital. Mahidol Univerisity ( Site 0213)
🇹🇭Bangkok Noi, Bangkok, Thailand
University of Kansas Cancer Center ( Site 0600)
🇺🇸Westwood, Kansas, United States
The University of Arizona Cancer Center - North Campus ( Site 0621)
🇺🇸Tucson, Arizona, United States
Georgetown University ( Site 0594)
🇺🇸Washington, District of Columbia, United States
Clinica Universidad Catolica del Maule ( Site 0065)
🇨🇱Talca, Region Del Maule, Chile
Fundacion Arturo Lopez Perez ( Site 0064)
🇨🇱Santiago, Region Metropolitana De Santiago, Chile
St Vincents Hospital Melbourne ( Site 0003)
🇦🇺Fitzroy, Victoria, Australia
BC Cancer-Vancouver Center ( Site 0056)
🇨🇦Vancouver, British Columbia, Canada
Instituto Clinico Oncologico del Sur ( Site 0067)
🇨🇱Temuco, Chile
Monash Health-Monash Medical Centre ( Site 0004)
🇦🇺Clayton, Victoria, Australia
Mater Misericordiae University Hospital ( Site 0241)
🇮🇪Dublin, Ireland
McGill University Health Centre ( Site 0052)
🇨🇦Montreal, Quebec, Canada
Fundacion Centro de Investigacion Clinica CIC ( Site 0141)
🇨🇴Medellin, Antioquia, Colombia
Biomelab S A S ( Site 0145)
🇨🇴Barranquilla, Atlantico, Colombia
Pontificia Universidad Catolica de Chile ( Site 0070)
🇨🇱Santiago, Region Metropolitana De Santiago, Chile
Administradora Country SA - Clinica del Country ( Site 0146)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Kurume University Hospital ( Site 0322)
🇯🇵Kurume, Fukuoka, Japan
Hospital General de Medellin Luz Castro de Gutierrez ( Site 0137)
🇨🇴Medellin, Antioquia, Colombia
Instituto Nacional de Cancerologia E.S.E ( Site 0142)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
National Cancer Center Hospital East ( Site 0306)
🇯🇵Kashiwa, Chiba, Japan
Kagawa University Hospital ( Site 0324)
🇯🇵Kita-gun, Kagawa, Japan
CRYPTEX Investigacion Clinica S.A. de C.V. ( Site 0362)
🇲🇽Mexico City, Mexico
St Vincents University Hospital ( Site 0242)
🇮🇪Dublin, Ireland
Aichi Cancer Center Hospital ( Site 0316)
🇯🇵Nagoya, Aichi, Japan
Medical Care and Research S.A. de C.V. ( Site 0359)
🇲🇽Merida, Mexico
Kagawa Prefectural Central Hospital ( Site 0325)
🇯🇵Takamatsu, Kagawa, Japan
Kyorin University Hospital ( Site 0309)
🇯🇵Mitaka, Tokyo, Japan
Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0304)
🇯🇵Sapporo, Hokkaido, Japan
Musashino Red Cross Hospital ( Site 0310)
🇯🇵Musashino, Tokyo, Japan
Kanagawa Cancer Center ( Site 0314)
🇯🇵Yokohama, Kanagawa, Japan
Wakayama Medical University Hospital ( Site 0318)
🇯🇵Wakayama, Japan
Centro de Investigacion Medica Aguascalientes ( Site 0355)
🇲🇽Aguascalientes, Mexico
ID Clinic ( Site 0431)
🇵🇱Myslowice, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0418)
🇵🇱Warszawa, Poland
N.N. Blokhin NMRCO ( Site 0439)
🇷🇺Moscow, Moskva, Russian Federation
Toranomon Hospital Kajigaya ( Site 0312)
🇯🇵Kawasaki, Kanagawa, Japan
Kindai University Hospital ( Site 0319)
🇯🇵Osakasayama, Osaka, Japan
Hiroshima University Hospital ( Site 0320)
🇯🇵Hiroshima, Japan
Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 0421)
🇵🇱Koszalin, Zachodniopomorskie, Poland
City Clinical Oncology Center ( Site 0446)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Pyatigorsk Oncology Dispensary ( Site 0441)
🇷🇺Pyatigorsk, Russian Federation
Taipei Veterans General Hospital ( Site 0524)
🇨🇳Taipei, Taiwan
MTZ Clinical Research Sp. z o. o. ( Site 0427)
🇵🇱Warsaw, Poland
First Moscow State Medical University n.a. I.M.Sechenov ( Site 0453)
🇷🇺Moscow, Moskva, Russian Federation
Chang Gung Medical Foundation. Linkou ( Site 0525)
🇨🇳Taoyuan, Taiwan
Istituto Oncologico Veneto ( Site 0287)
🇮🇹Padova, Italy
CHRU de Lille - Hopital Claude Huriez ( Site 0159)
🇫🇷Lille, France
Scripps Health ( Site 0644)
🇺🇸La Jolla, California, United States
City of Hope Comprehensive Cancer Center ( Site 0587)
🇺🇸Duarte, California, United States
Pacific Hematology Oncology Associates ( Site 0588)
🇺🇸San Francisco, California, United States
UCLA ( Site 0589)
🇺🇸Santa Monica, California, United States
Tampa General Medical Group ( Site 0629)
🇺🇸Tampa, Florida, United States
University of Rochester ( Site 0613)
🇺🇸Rochester, New York, United States
Icahn School of Medicine at Mount Sinai ( Site 0611)
🇺🇸New York, New York, United States
Advent Health ( Site 0595)
🇺🇸Orlando, Florida, United States
University of Oklahoma Health Science Center ( Site 0625)
🇺🇸Oklahoma City, Oklahoma, United States
Stony Brook University Medical Center - Cancer Center ( Site 0612)
🇺🇸Stony Brook, New York, United States
Oregon Health & Science University ( Site 0645)
🇺🇸Portland, Oregon, United States
Eastern Regional Medical Center, Inc. ( Site 0626)
🇺🇸Philadelphia, Pennsylvania, United States
Central Texas Veterans Healthcare System ( Site 0617)
🇺🇸Temple, Texas, United States
Royal Prince Alfred Hospital ( Site 0001)
🇦🇺Camperdown, New South Wales, Australia
Cancer Care Northwest ( Site 0636)
🇺🇸Spokane, Washington, United States
Princess Margaret Cancer Centre ( Site 0050)
🇨🇦Toronto, Ontario, Canada
First Affiliated Hospital of Anhui Medical University ( Site 0095)
🇨🇳Hefei, Anhui, China
Sunnybrook Research Institute ( Site 0055)
🇨🇦Toronto, Ontario, Canada
London Health Sciences Centre ( Site 0053)
🇨🇦London, Ontario, Canada
Liverpool Hospital. ( Site 0002)
🇦🇺Liverpool, Australia
Cancer Hospital Chinese Academy of Medical Sciences ( Site 0100)
🇨🇳Beijing, Beijing, China
Southern Medical University Nanfang Hospital ( Site 0102)
🇨🇳Guangzhou, Guangdong, China
Wuhan Union hospital Cancer Center ( Site 0105)
🇨🇳Wuhan, Hubei, China
Harbin Medical University Cancer Hospital ( Site 0089)
🇨🇳Harbin, Heilongjiang, China
Beijing Cancer Hospital ( Site 0088)
🇨🇳Beijing, Beijing, China
Hunan Cancer Hospital ( Site 0094)
🇨🇳Changsha, Hunan, China
The Third Xiangya Hospital of Central South University ( Site 0093)
🇨🇳Changsha, Hunan, China
The 81st Hospital of PLA ( Site 0085)
🇨🇳Nanjing, Jiangsu, China
West China Hospital of Sichuan University ( Site 0087)
🇨🇳Chengdu, Sichuan, China
Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0109)
🇨🇳Urumqi, Xinjiang, China
Fudan University Shanghai Cancer Center ( Site 0086)
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Xi an Jiaotong University ( Site 0090)
🇨🇳XI An, Shanxi, China
Sir Run Run Shaw Hospital ( Site 0110)
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Zhejiang University ( Site 0097)
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Cancer Hospital ( Site 0101)
🇨🇳Hangzhou, Zhejiang, China
Hospital Pablo Tobon Uribe ( Site 0144)
🇨🇴Medellin, Antioquia, Colombia
Zhongshan Hospital Fudan University ( Site 0096)
🇨🇳Shanghai, China
Institut Sainte Catherine ( Site 0167)
🇫🇷Avignon, France
Hopital Beaujon ( Site 0160)
🇫🇷Clichy, France
Fundacion Valle del Lili ( Site 0140)
🇨🇴Cali, Valle Del Cauca, Colombia
CHU Henri Mondor ( Site 0162)
🇫🇷Creteil, France
Hopital de la Croix Rousse ( Site 0157)
🇫🇷Lyon, France
Centre Hospitalier Regional du Orleans ( Site 0169)
🇫🇷Orleans, France
Centre Eugene Marquis ( Site 0158)
🇫🇷Rennes, France
CHU de Nancy Hopital Brabois Adultes ( Site 0164)
🇫🇷Vandoeuvre les Nancy, France
Hopital Saint Joseph ( Site 0166)
🇫🇷Marseille, France
Universitaetsklinikum Essen ( Site 0188)
🇩🇪Essen, Germany
Universitaetsklinikum Carl Gustav Carus der TU Dresden ( Site 0178)
🇩🇪Dresden, Germany
Klinikum der Universitaet Aachen - RWTH ( Site 0185)
🇩🇪Aachen, Germany
Universitaetsklinikum Frankfurt ( Site 0180)
🇩🇪Frankfurt am Main, Germany
Universitaetsklinikum Hamburg-Eppendorf ( Site 0184)
🇩🇪Hamburg, Germany
Universitaetsklinikum Leipzig ( Site 0187)
🇩🇪Leipzig, Germany
Universitaetsklinik Koeln ( Site 0189)
🇩🇪Koeln, Germany
Universitaetsklinikum Tuebingen ( Site 0179)
🇩🇪Tuebingen, Germany
Universitaetsklinikum Wuerzburg ( Site 0186)
🇩🇪Wuerzburg, Germany
Otto-Von-Guericke-Universitaet Magdeburg ( Site 0182)
🇩🇪Magdeburg, Germany
Ospedale Sacro Cuore - Don Calabria ( Site 0289)
🇮🇹Negrar, VR, Italy
Centro di Riferimento Oncologico de Aviano Istituto Nazionale Tumori ( Site 0292)
🇮🇹Aviano, Italy
Policlinico S. Orsola-Malpighi ( Site 0286)
🇮🇹Bologna, Italy
Az Osp Univ Policlin Paolo Giaccone ( Site 0284)
🇮🇹Palermo, Italy
Fondazione Salvatore Maugeri IRCCS. ( Site 0290)
🇮🇹Pavia, Italy
Azienda Ospedaliero-Univers. Pisana Ospedale S. Chiara ( Site 0291)
🇮🇹Pisa, Italy
Policlinico Universitario Campus Biomedico ( Site 0288)
🇮🇹Roma, Italy
Kanazawa University Hospital ( Site 0315)
🇯🇵Kanazawa, Ishikawa, Japan
Yokohama City University Medical Center ( Site 0313)
🇯🇵Yokohama, Kanagawa, Japan
Chiba University Hospital ( Site 0305)
🇯🇵Chiba, Japan
National Hospital Organization Kyushu Medical Center ( Site 0321)
🇯🇵Fukuoka, Japan
National Cancer Center Hospital ( Site 0307)
🇯🇵Tokyo, Japan
Osaka Red Cross Hospital ( Site 0317)
🇯🇵Osaka, Japan
Saga-Ken Medical Centre Koseikan ( Site 0323)
🇯🇵Saga, Japan
The University of Tokyo Hospital ( Site 0308)
🇯🇵Tokyo, Japan
Toranomon Hospital ( Site 0311)
🇯🇵Tokyo, Japan
Seoul National University Bundang Hospital ( Site 0464)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Yonsei University Severance Hospital ( Site 0463)
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Asan Medical Center ( Site 0460)
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Seoul National University Hospital ( Site 0462)
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0363)
🇲🇽Ciudad de Mexico, Cdmx, Mexico
Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0365)
🇲🇽Guadalajara, Jalisco, Mexico
Oaxaca Site Management Organization S.C. ( Site 0366)
🇲🇽Oaxaca, Mexico
Christchurch Hospital ( Site 0377)
🇳🇿Christchurch, New Zealand
Unidad Medica Oncologica ( Site 0369)
🇲🇽Puebla, Mexico
Auckland City Hospital ( Site 0376)
🇳🇿Auckland, New Zealand
Railway Hospital of OJSC ( Site 0447)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Hospital Universitari Vall d Hebron ( Site 0508)
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Hospital Universitario Puerta de Hierro ( Site 0513)
🇪🇸Majadahonda, Madrid, Spain
Complejo Hospitalario Universitario de Santiago ( Site 0506)
🇪🇸Santiago de Compostela, Spain
Hospital Universitario Virgen del Rocio ( Site 0509)
🇪🇸Sevilla, Spain
Kaohsiung Medical University Chung-Ho Memorial Hospital ( Site 0529)
🇨🇳Kaoshiung, Taiwan
Taichung Veterans General Hospital ( Site 0526)
🇨🇳Taichung, Taiwan
Hospital Universitario y Politecnico La Fe de Valencia ( Site 0505)
🇪🇸Valencia, Spain
China Medical University Hospital ( Site 0527)
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital ( Site 0528)
🇨🇳Tainan, Taiwan
Chiang Mai University Maharaj Nakorn Chiang Mai Hospital ( Site 0211)
🇹🇭Chiang Mai, Thailand
Adana Sehir Hastanesi ( Site 0549)
🇹🇷Adana, Turkey
Hacettepe Uni. Tip Fakultesi ( Site 0553)
🇹🇷Ankara, Turkey
Akdeniz Universitesi Tip Fakultesi ( Site 0548)
🇹🇷Antalya, Turkey
Songklanagarind Hospital ( Site 0214)
🇹🇭HatYai, Songkhla, Thailand
Bezmi Alem Universitesi Tıp Fakultesi ( Site 0547)
🇹🇷İstanbul, Turkey
Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 0550)
🇹🇷Konya, Turkey
Trakya Universitesi Tip Fakultesi ( Site 0544)
🇹🇷Edirne, Turkey
Erzurum Ataturk University Faculty of Medicine ( Site 0546)
🇹🇷Erzurum, Turkey
Royal Free London NHS Foundation Trust ( Site 0567)
🇬🇧London, London, City Of, United Kingdom
Kings College Hospital NHS Foundation Trust ( Site 0565)
🇬🇧London, London, City Of, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0573)
🇬🇧Birkenhead, United Kingdom
The Beatson West of Scotland Cancer Centre ( Site 0566)
🇬🇧Glasgow, United Kingdom
The Christie NHS Foundation Trust ( Site 0575)
🇬🇧Manchester, United Kingdom
Nottingham University Hospitals NHS Trust ( Site 0569)
🇬🇧Nottingham, United Kingdom
Samsung Medical Center ( Site 0461)
🇰🇷Seoul, Korea, Republic of
Hospital General Universitario Gregorio Maranon ( Site 0504)
🇪🇸Madrid, Spain
Centro Medico Imbanaco de Cali S.A ( Site 0139)
🇨🇴Cali, Valle Del Cauca, Colombia