Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) Plus Chemotherapy in Participants With Advanced/Metastatic Gastroesophageal Adenocarcinoma (MK-7902-015/E7080-G000-321/LEAP-015)
- Conditions
- Advanced/Metastatic Gastroesophageal Adenocarcinoma
- Interventions
- Registration Number
- NCT04662710
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to assess the efficacy and safety of lenvatinib (E7080/MK-7902) plus pembrolizumab (MK-3475) plus chemotherapy compared with chemotherapy alone in participants with advanced/metastatic gastroesophageal cancer.
The primary study hypotheses are that lenvatinib plus pembrolizumab plus chemotherapy is superior to chemotherapy alone for both overall survival (OS) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), in participants with programmed cell death-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 and in all participants.
- Detailed Description
There will be 2 parts to the study: a Safety Run-in (Part 1) and the Main Study (Part 2). In Part 1 (Safety Run-in), approximately 12 participants will be treated with lenvatinib in combination with pembrolizumab and chemotherapy with either capecitabine and oxaliplatin (CAPOX), or 5-fluorouracil (5-FU), Leucovorin, and oxaliplatin (mFOLFOX6). Participants will be closely followed for dose-limiting toxicities for 21 days after the first dose of study intervention.
In Part 2, up to 878 eligible participants (not including those participating in Part 1) will be randomly assigned in a 1:1 ratio to either lenvatinib plus pembrolizumab plus chemotherapy (CAPOX or mFOLFOX6) or Chemotherapy alone (CAPOX or mFOLFOX6).
Participants can receive up to 18 infusions (up to 2 years) of pembrolizumab in the first course. Participants may be eligible to receive a second course of pembrolizumab (approximately 1 year) at the investigator's discretion.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 895
- Has histologically and/or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic gastroesophageal adenocarcinoma
- Is not expected to require tumor resection during the treatment course
- Has gastroesophageal adenocarcinoma that is not HER-2/neu positive
- Has measurable disease as defined by RECIST 1.1 by scan with IV contrast as determined by the local site investigator
- Male participants agree to refrain from donating sperm and agree to either remain abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for ≥7 days after last dose of lenvatinib or 90 days after last dose of chemotherapy-whichever comes last
- Female participants not pregnant or breastfeeding are eligible to participate if not a women of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle, and do not donate eggs (ova, oocytes) to others or freeze/store for their own use, and abstain from breastfeeding during the intervention period through 120 days after last dose of pembrolizumab, 30 days after last dose of lenvatinib, or 180 days after last dose of chemotherapy-whichever occurs last
- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of study treatment
- Has adequately controlled blood pressure with or without antihypertensive medications
- Has adequate organ function
- Has had previous therapy for locally advanced unresectable or metastatic gastric/gastroesophageal junction (GEJ) esophageal adenocarcinoma
- Has had major surgery within 28 days prior to first dose of study interventions
- Has had radiotherapy within 14 days of randomization
- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
- Has known CNS metastases and/or carcinomatous meningitis
- Has severe hypersensitivity (≥Grade 3) to treatment with an monoclonal antibody (mAb) or known sensitivity or intolerance to any component of lenvatinib, pembrolizumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum containing products
- Has had an allogeneic tissue/solid organ transplant
- Has perforation risks or significant gastrointestinal (GI) bleeding
- Has GI obstruction, poor oral intake (CAPOX participants), or difficulty in taking oral medication (CAPOX participants)
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
- Has received prior therapy with anti- vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor or anti-VEGF mAb
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
- Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
- Has inadequate cardiac function
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- Has poorly controlled diarrhea
- Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment.
- Has peripheral neuropathy ≥Grade 2
- Has a known history of human immunodeficiency virus (HIV) or HIV 1/2 antibodies
- Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
- Has weight loss of >20% within the last 3 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chemotherapy Leucovorin (or Levoleucovorin) Participants receive chemotherapy with either CAPOX Q3W or mFOLFOX6 Q2W. A cycle is 6 weeks (42 days). Lenvatinib + Pembrolizumab + Chemotherapy Lenvatinib Participants receive lenvatinib administered orally (PO) every day (QD) in combination with pembrolizumab intravenously (IV) every 6 weeks (Q6W) plus chemotherapy with either capecitabine and oxaliplatin (CAPOX) or chemotherapy with 5-FU, leucovorin, and oxaliplatin (mFOLFOX6). Induction with lenvatinib 8 mg QD plus pembrolizumab (400 mg Q6W) plus chemotherapy (CAPOX or mFOLFOX6) will be administered for 2 cycles (approximately 12 weeks), followed by consolidation with lenvatinib 20 mg QD plus pembrolizumab (400 mg Q6W) for 16 cycles. A cycle is 6 weeks (42 days). Lenvatinib + Pembrolizumab + Chemotherapy Leucovorin (or Levoleucovorin) Participants receive lenvatinib administered orally (PO) every day (QD) in combination with pembrolizumab intravenously (IV) every 6 weeks (Q6W) plus chemotherapy with either capecitabine and oxaliplatin (CAPOX) or chemotherapy with 5-FU, leucovorin, and oxaliplatin (mFOLFOX6). Induction with lenvatinib 8 mg QD plus pembrolizumab (400 mg Q6W) plus chemotherapy (CAPOX or mFOLFOX6) will be administered for 2 cycles (approximately 12 weeks), followed by consolidation with lenvatinib 20 mg QD plus pembrolizumab (400 mg Q6W) for 16 cycles. A cycle is 6 weeks (42 days). Chemotherapy Capecitabine Participants receive chemotherapy with either CAPOX Q3W or mFOLFOX6 Q2W. A cycle is 6 weeks (42 days). Lenvatinib + Pembrolizumab + Chemotherapy Oxaliplatin Participants receive lenvatinib administered orally (PO) every day (QD) in combination with pembrolizumab intravenously (IV) every 6 weeks (Q6W) plus chemotherapy with either capecitabine and oxaliplatin (CAPOX) or chemotherapy with 5-FU, leucovorin, and oxaliplatin (mFOLFOX6). Induction with lenvatinib 8 mg QD plus pembrolizumab (400 mg Q6W) plus chemotherapy (CAPOX or mFOLFOX6) will be administered for 2 cycles (approximately 12 weeks), followed by consolidation with lenvatinib 20 mg QD plus pembrolizumab (400 mg Q6W) for 16 cycles. A cycle is 6 weeks (42 days). Lenvatinib + Pembrolizumab + Chemotherapy Capecitabine Participants receive lenvatinib administered orally (PO) every day (QD) in combination with pembrolizumab intravenously (IV) every 6 weeks (Q6W) plus chemotherapy with either capecitabine and oxaliplatin (CAPOX) or chemotherapy with 5-FU, leucovorin, and oxaliplatin (mFOLFOX6). Induction with lenvatinib 8 mg QD plus pembrolizumab (400 mg Q6W) plus chemotherapy (CAPOX or mFOLFOX6) will be administered for 2 cycles (approximately 12 weeks), followed by consolidation with lenvatinib 20 mg QD plus pembrolizumab (400 mg Q6W) for 16 cycles. A cycle is 6 weeks (42 days). Lenvatinib + Pembrolizumab + Chemotherapy 5-FU Participants receive lenvatinib administered orally (PO) every day (QD) in combination with pembrolizumab intravenously (IV) every 6 weeks (Q6W) plus chemotherapy with either capecitabine and oxaliplatin (CAPOX) or chemotherapy with 5-FU, leucovorin, and oxaliplatin (mFOLFOX6). Induction with lenvatinib 8 mg QD plus pembrolizumab (400 mg Q6W) plus chemotherapy (CAPOX or mFOLFOX6) will be administered for 2 cycles (approximately 12 weeks), followed by consolidation with lenvatinib 20 mg QD plus pembrolizumab (400 mg Q6W) for 16 cycles. A cycle is 6 weeks (42 days). Chemotherapy Oxaliplatin Participants receive chemotherapy with either CAPOX Q3W or mFOLFOX6 Q2W. A cycle is 6 weeks (42 days). Chemotherapy 5-FU Participants receive chemotherapy with either CAPOX Q3W or mFOLFOX6 Q2W. A cycle is 6 weeks (42 days). Lenvatinib + Pembrolizumab + Chemotherapy Pembrolizumab Participants receive lenvatinib administered orally (PO) every day (QD) in combination with pembrolizumab intravenously (IV) every 6 weeks (Q6W) plus chemotherapy with either capecitabine and oxaliplatin (CAPOX) or chemotherapy with 5-FU, leucovorin, and oxaliplatin (mFOLFOX6). Induction with lenvatinib 8 mg QD plus pembrolizumab (400 mg Q6W) plus chemotherapy (CAPOX or mFOLFOX6) will be administered for 2 cycles (approximately 12 weeks), followed by consolidation with lenvatinib 20 mg QD plus pembrolizumab (400 mg Q6W) for 16 cycles. A cycle is 6 weeks (42 days).
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants with Adverse Events (AEs) Up to ~28 months An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 1 with AEs will be reported by treatment arm.
Part 1: Number of Participants who Discontinued Study Treatment Due to an AE Up to ~25 months An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 1 that discontinued study due to an AE will be reported by treatment arm.
Part 2: PFS Per RECIST 1.1 as Assessed by BICR in All Participants Up to ~31 months PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS will be reported by treatment arm for all participants in Part 2.
Part 2: OS in All Participants Up to ~41 months OS is defined as the time from randomization to death due to any cause. OS will be reported by treatment arm for all participants in Part 2.
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) Up to ~21 days Hematologic DLTs were defined as Grade 4 neutropenia lasting for ≥7 days, Grade 3 or Grade 4 febrile neutropenia, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia, or Grade 4 anemia. Other nonhematologic toxicities considered a DLT included any other Grade 4 or Grade 5 toxicity, Grade 3 toxicities lasting \>3 days (excluding nausea, vomiting, and diarrhea controlled by medical intervention within 72 hours, and Grade 3 rash in the absence of desquamation with no mucosal involvement), Grade 3 hypertension not able to be controlled by medication, ≥Grade 3 gastrointestinal perforation, ≥Grade 3 wound dehiscence requiring medical or surgical intervention, or any grade thromboembolic event. The number of participants in Part 1 with DLTs will be reported by treatment arm.
Part 2: Overall Survival (OS) in Participants with Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Up to ~41 months OS is defined as the time from randomization to death due to any cause. OS will be reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.
Part 2: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1 CPS ≥1 Up to ~31 months PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. PFS will be reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.
- Secondary Outcome Measures
Name Time Method Part 2: ORR Per RECIST 1.1 as Assessed by BICR in All Participants Up to ~31 months ORR is defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and assessed by BICR. ORR will be reported by treatment arm for all participants in Part 2.
Part 2: DOR Per RECIST 1.1 as Assessed by BICR in All Participants Up to ~31 months For participants who demonstrated confirmed CR or PR, DOR is defined as the time from the first CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) to subsequent PD or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR will be reported by treatment arm for all participants in Part 2.
Part 2: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1 Up to ~31 months ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and assessed by BICR. ORR will be reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.
Part 2: Number of Participants with AEs Up to ~28 months An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 2 with AEs will be reported by treatment arm.
Part 2: Number of Participants who Discontinued Study Treatment Due to an AE Up to ~25 months An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants in Part 2 that discontinued study due to an AE will be reported by treatment arm.
Part 2: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants with PD-L1 CPS ≥1 Up to ~31 months For participants who demonstrated confirmed CR or PR, DOR is defined as the time from the first CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) to subsequent PD or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR will be reported by treatment arm for PD-L1 CPS ≥1 participants in Part 2.
Trial Locations
- Locations (177)
UCLA Hematology/Oncology - Santa Monica ( Site 0003)
🇺🇸Los Angeles, California, United States
Nepean Hospital ( Site 2305)
🇦🇺Kingswood, New South Wales, Australia
Mount Sinai Hospital ( Site 0051)
🇺🇸New York, New York, United States
Georgetown University Medical Center ( Site 0009)
🇺🇸Washington, District of Columbia, United States
Washington University School of Medicine ( Site 0027)
🇺🇸Saint Louis, Missouri, United States
AHN West Penn Hospital-AHN Esophageal and Lung Institute ( Site 0058)
🇺🇸Pittsburgh, Pennsylvania, United States
Fundacion Favaloro ( Site 0201)
🇦🇷Buenos Aires, Argentina
Memorial Sloan Kettering Cancer Center ( Site 0032)
🇺🇸New York, New York, United States
Cancer Hospital Chinese Academy of Medical Sciences ( Site 2403)
🇨🇳Beijing, Beijing, China
Hamilton Health Sciences - Juravinski Site ( Site 0106)
🇨🇦Hamilton, Ontario, Canada
Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0207)
🇦🇷Buenos Aires, Argentina
First Hospital of Lanzhou University ( Site 2417)
🇨🇳Lanzhou, Gansu, China
Johns Hopkins University ( Site 0052)
🇺🇸Baltimore, Maryland, United States
Shanghai General Hospital ( Site 2424)
🇨🇳Shanghai, Shanghai, China
Hubei Cancer Hospital ( Site 2429)
🇨🇳Wuhan, Hubei, China
CHU UCL Namur Site de Godinne ( Site 1005)
🇧🇪Yvoir, Namur, Belgium
Royal Brisbane and Women s Hospital ( Site 2304)
🇦🇺Herston, Queensland, Australia
Anhui Provincial Hospital ( Site 2415)
🇨🇳Hefei, Anhui, China
Wollongong Hospital ( Site 2307)
🇦🇺Wollongong, New South Wales, Australia
CHU Bordeaux Haut-Leveque ( Site 1110)
🇫🇷Pessac, Gironde, France
Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2428)
🇨🇳Urumqi, Xinjiang, China
Medizinische Hochschule Hannover ( Site 1210)
🇩🇪Hannover, Niedersachsen, Germany
Hopital Saint Louis ( Site 1100)
🇫🇷Paris, France
A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1604)
🇮🇹Napoli, Italy
Centre Georges Francois Leclerc ( Site 1106)
🇫🇷Dijon, Cote-d Or, France
Samsung Medical Center ( Site 2801)
🇰🇷Seoul, Korea, Republic of
Institut du Cancer Avignon-Provence ( Site 1103)
🇫🇷Avignon, Vaucluse, France
Centre Francois Baclesse ( Site 1107)
🇫🇷Caen, Calvados, France
Charite Berlin Campus Virchow-Klinikum ( Site 1202)
🇩🇪Berlin, Germany
Presidio Ospedaliero Universitario Santa Maria della Misericordia ( Site 1609)
🇮🇹Udine, Friuli-Venezia Giulia, Italy
Hôpital Edouard Herriot ( Site 1116)
🇫🇷Lyon, Rhone-Alpes, France
CHU Hopital Saint Antoine ( Site 1102)
🇫🇷Paris, France
IRCCS Ospedale San Raffaele di Milano ( Site 1603)
🇮🇹Milano, Italy
Facharztzentrum Eppendorf ( Site 1201)
🇩🇪Hamburg, Germany
Klinikum Rechts der Isar der TU Muenchen ( Site 1200)
🇩🇪Muechen, Bayern, Germany
Universitaetsklinikum Leipzig ( Site 1211)
🇩🇪Leipzig, Sachsen, Germany
Kobe City Medical Center General Hospital ( Site 2606)
🇯🇵Kobe, Hyogo, Japan
Kagawa University Hospital ( Site 2611)
🇯🇵Kita-gun, Kagawa, Japan
Azienda Ospedaliera Mater Domini-Translational Oncology Unit ( Site 1611)
🇮🇹Catanzaro, Italy
Hyogo Cancer Center ( Site 2621)
🇯🇵Akashi, Hyogo, Japan
Kansai Medical University Hospital ( Site 2622)
🇯🇵Hirakata, Osaka, Japan
Saitama Cancer Center ( Site 2604)
🇯🇵Kitaadachi-gun, Saitama, Japan
Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1702)
🇵🇱Przemysl, Podkarpackie, Poland
Konyang University ( Site 2807)
🇰🇷Daejeon, Taejon-Kwangyokshi, Korea, Republic of
Przychodnia Lekarska KOMED ( Site 1701)
🇵🇱Konin, Wielkopolskie, Poland
China Medical University Hospital ( Site 2903)
🇨🇳Taichung, Taiwan
Ninewells Hospital and Medical School ( Site 2207)
🇬🇧Dundee, Dundee City, United Kingdom
Royal Marsden NHS Foundation Trust ( Site 2202)
🇬🇧London, London, City Of, United Kingdom
Beijing Cancer Hospital ( Site 2453)
🇨🇳Beijing, Beijing, China
Fujian Provincial Cancer Hospital ( Site 2408)
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University ( Site 2420)
🇨🇳Xiamen, Fujian, China
The First Affiliated Hospital of Xiamen University ( Site 2446)
🇨🇳Xiamen, Fujian, China
Hunan Cancer Hospital ( Site 2440)
🇨🇳Changsha, Hunan, China
Changzhou Cancer Hospital-Department of Oncology ( Site 2458)
🇨🇳Changzhou, Jiangsu, China
Zhongshan Hospital Affiliated to Xiamen University ( Site 2421)
🇨🇳Xiamen, Fujian, China
Nanfang Hospital ( Site 2456)
🇨🇳Guangzhou, Guangdong, China
The Affiliated Hospital Of Hainan Medical University-Cancer rehabilitation and palliative treatment
🇨🇳Haikou, Hainan, China
Fourth Hospital Of Hebei Medical University ( Site 2441)
🇨🇳Shijiazhuang, Hebei, China
Harbin Medical University Cancer Hospital ( Site 2410)
🇨🇳Harbin, Heilongjiang, China
Nantong Tumor Hospital-Digestive Oncology ( Site 2464)
🇨🇳Nantong, Jiangsu, China
Jilin Cancer Hospital ( Site 2438)
🇨🇳Changchun, Jilin, China
Nanjing Drum Tower Hospital ( Site 2419)
🇨🇳Nanjing, Jiangsu, China
Tang Du Hospital ( Site 2432)
🇨🇳XI An, Shaanxi, China
Tianjin Medical University Cancer Institute & Hospital ( Site 2447)
🇨🇳Tianjin, Tianjin, China
Shanghai East Hospital ( Site 2455)
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Zhejiang University ( Site 2414)
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital ( Site 2412)
🇨🇳Hangzhou, Zhejiang, China
Hospital General Universitari Vall d Hebron ( Site 1907)
🇪🇸Barcelona, Spain
Centre Hospitalier Annecy Genevois ( Site 1117)
🇫🇷Epagny Metz-Tessy, Haute-Savoie, France
Hollywood Private Hospital-Medical Oncology ( Site 2308)
🇦🇺Nedlands, Western Australia, Australia
Clinica Universidad Catolica del Maule ( Site 0411)
🇨🇱Talca, Maule, Chile
UMASS Memorial Medical Center ( Site 0020)
🇺🇸Worcester, Massachusetts, United States
AZ Delta ( Site 1006)
🇧🇪Roeselare, West-Vlaanderen, Belgium
UZ Gent ( Site 1002)
🇧🇪Gent, Oost-Vlaanderen, Belgium
Centro Investigación del Cáncer James Lind ( Site 0414)
🇨🇱Temuco, Araucania, Chile
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0103)
🇨🇦Sherbrooke, Quebec, Canada
The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Si
🇨🇳Fuzhou, Fujian, China
Henan Cancer Hospital ( Site 2443)
🇨🇳Zhengzhou, Henan, China
LinYi Cancer Hospital-Gastrology department ( Site 2463)
🇨🇳Linyi, Shandong, China
Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 0602)
🇨🇷Santa Ana, San Jose, Costa Rica
Krankenhaus Nordwest ( Site 1205)
🇩🇪Frankfurt am Main, Hessen, Germany
Universitaetsklinikum Regensburg ( Site 1203)
🇩🇪Regensburg, Bayern, Germany
St James Hospital ( Site 1400)
🇮🇪Dublin, Leinster, Ireland
Rabin Medical Center ( Site 1506)
🇮🇱Petah Tikva, Israel
Humanitas Research Hospital ( Site 1600)
🇮🇹Rozzano, Lombardia, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1610)
🇮🇹Milan, Lombardia, Italy
Kindai University Hospital ( Site 2600)
🇯🇵Osakasayama, Osaka, Japan
Ibaraki Prefectural Central Hospital ( Site 2618)
🇯🇵Kasama, Ibaraki, Japan
National Hospital Organization Kyushu Cancer Center ( Site 2609)
🇯🇵Fukuoka, Japan
The Cancer Institute Hospital of JFCR ( Site 2605)
🇯🇵Tokyo, Japan
Hiroshima City Hiroshima Citizens Hospital ( Site 2612)
🇯🇵Hiroshima, Japan
Osaka International Cancer Institute ( Site 2607)
🇯🇵Osaka, Japan
Hallym University Sacred Heart Hospital ( Site 2806)
🇰🇷Anyang-si, Kyonggi-do, Korea, Republic of
Asan Medical Center ( Site 2802)
🇰🇷Songpagu, Seoul, Korea, Republic of
Seoul National University Bundang Hospital ( Site 2804)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Seoul National University Hospital ( Site 2803)
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 2800)
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital ( Site 2805)
🇰🇷Seoul, Korea, Republic of
Dolnoslaskie Centrum Onkologii. ( Site 1712)
🇵🇱Wroclaw, Dolnoslaskie, Poland
Korea University Guro Hospital ( Site 2808)
🇰🇷Seoul, Korea, Republic of
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 1704)
🇵🇱Warszawa, Mazowieckie, Poland
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1816)
🇷🇺Chelyabinsk, Chelyabinskaya Oblast, Russian Federation
Szpital Kliniczny im. Heliodora Swiecickiego Uniwers Medyczn ( Site 1703)
🇵🇱Poznan, Wielkopolskie, Poland
National Medical and Surgical Center n.a.N.I.Pirogov ( Site 1805)
🇷🇺Moscow, Moskva, Russian Federation
Blokhin National Medical Oncology ( Site 1800)
🇷🇺Moscow, Moskva, Russian Federation
Central Clinical Hospital with Polyclinic ( Site 1801)
🇷🇺Moscow, Moskva, Russian Federation
Medical University REAVIZ ( Site 1814)
🇷🇺Samara, Samarskaya Oblast, Russian Federation
St Petersburg City Clinical Oncology Dispensary ( Site 1808)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Leningrad Regional Oncology Center ( Site 1810)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1809)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Hospital Universitario General de Asturias ( Site 1901)
🇪🇸Oviedo, Asturias, Spain
Hospital Universitario Marques de Valdecilla ( Site 1902)
🇪🇸Santander, Cantabria, Spain
Sakarya Universitesi Tip Fakultesi ( Site 2007)
🇹🇷Sakarya, Istanbul, Turkey
Hospital General Gregorio Maranon de Madrid ( Site 1904)
🇪🇸Madrid, Spain
Chang Gung Medical Foundation. Linkou ( Site 2902)
🇨🇳Taoyuan, Taiwan
National Taiwan University Hospital ( Site 2901)
🇨🇳Taipei, Taiwan
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2003)
🇹🇷Ankara, Turkey
Memorial Ankara Hastanesi ( Site 2004)
🇹🇷Ankara, Turkey
Trakya Universitesi Tip Fakultesi ( Site 2000)
🇹🇷Edirne, Turkey
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2002)
🇹🇷Istanbul, Turkey
Ege Universitesi Tip Fakultesi Hastanesi ( Site 2001)
🇹🇷Izmir, Turkey
Addenbrooke's Hospital ( Site 2200)
🇬🇧Cambridge, Cambridgeshire, United Kingdom
The Beatson West of Scotland Cancer Centre ( Site 2204)
🇬🇧Glasgow, Glasgow City, United Kingdom
University College London Hospitals NHS Foundation Trust ( Site 2201)
🇬🇧London, London, City Of, United Kingdom
University Hospital Coventry and Warwickshire NHS Trust ( Site 2205)
🇬🇧Coventry, Warwickshire, United Kingdom
Royal Marsden NHS Trust ( Site 2203)
🇬🇧Sutton, Surrey, United Kingdom
The Christie NHS Foundation Trust ( Site 2209)
🇬🇧Manchester, United Kingdom
James Graham Brown Cancer Center ( Site 0017)
🇺🇸Louisville, Kentucky, United States
Henry Ford Health System ( Site 0023)
🇺🇸Detroit, Michigan, United States
Oncologika S.A. ( Site 0704)
🇬🇹Guatemala, Guatemala
Clinica Privada Dr Rixci Ramirez Fallas ( Site 0702)
🇬🇹Guatemala, Guatemala
Sanatorio Nuestra Senora del Pilar ( Site 0705)
🇬🇹Guatemala, Guatemala
Medi-K Cayala ( Site 0700)
🇬🇹Guatemala, Guatemala
Soroka Medical Center ( Site 1507)
🇮🇱Be'er Sheva, Israel
Hillel Yaffe Medical Center ( Site 1503)
🇮🇱Hadera, Israel
Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1608)
🇮🇹Meldola, Abruzzo, Italy
Aichi Cancer Center Hospital ( Site 2603)
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East ( Site 2601)
🇯🇵Kashiwa, Chiba, Japan
Kanagawa Cancer Center ( Site 2608)
🇯🇵Yokohama, Kanagawa, Japan
National Cancer Center Hospital ( Site 2602)
🇯🇵Tokyo, Japan
Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1821)
🇷🇺Yaroslavl, Yaroslavskaya Oblast, Russian Federation
Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2005)
🇹🇷Erzurum, Turkey
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0508)
🇨🇴Valledupar, Cesar, Colombia
IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 0202)
🇦🇷Caba, Buenos Aires, Argentina
Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0407)
🇨🇱Santiago, Region M. De Santiago, Chile
Bradfordhill ( Site 0404)
🇨🇱Santiago, Region M. De Santiago, Chile
CIMCA-Hemato-Oncology ( Site 0601)
🇨🇷San José, San Jose, Costa Rica
Soluciones Gastrointestinales S.A. ( Site 0706)
🇬🇹Guatemala, Guatemala
Rambam Health Care Campus-Oncology Division ( Site 1502)
🇮🇱Haifa, Israel
Meir Medical Center ( Site 1504)
🇮🇱Kfar-Saba, Israel
Sourasky Medical Center ( Site 1500)
🇮🇱Tel Aviv, Israel
National Hospital Organization Shikoku Cancer Center ( Site 2610)
🇯🇵Matsuyama, Ehime, Japan
Dana Farber Cancer Center ( Site 0019)
🇺🇸Boston, Massachusetts, United States
Cancer and Hematology Centers of Western Michigan ( Site 0025)
🇺🇸Grand Rapids, Michigan, United States
Queen Elizabeth II Health Sciences Centre ( Site 0101)
🇨🇦Halifax, Nova Scotia, Canada
CEMIC ( Site 0209)
🇦🇷Buenos Aires, Argentina
UZ Leuven ( Site 1004)
🇧🇪Leuven, Vlaams-Brabant, Belgium
Oncomedica S.A. ( Site 0507)
🇨🇴Monteria, Cordoba, Colombia
Hopital Henri Mondor ( Site 1105)
🇫🇷Creteil, Val-de-Marne, France
Princess Margaret Hospital. ( Site 2502)
🇭🇰Hong Kong, Hong Kong
Beaumont Hospital ( Site 1402)
🇮🇪Dublin, Ireland
National Cheng Kung University Hospital ( Site 2904)
🇨🇳Tainan, Taiwan
Instituto Cancerologico de Narino Ltda ( Site 0504)
🇨🇴Pasto, Narino, Colombia
Instituto Medico Alexander Fleming ( Site 0208)
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Hospital Aleman ( Site 0210)
🇦🇷Buenos Aires, Argentina
Hospital Privado de Cordoba ( Site 0204)
🇦🇷Cordoba, Argentina
Fundacion Arturo Lopez Perez FALP ( Site 0403)
🇨🇱Santiago, Region M. De Santiago, Chile
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0501)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Oncomedica ( Site 0701)
🇬🇹Guatemala, Guatemala
Clinica de la Costa S.A.S. ( Site 0502)
🇨🇴Barranquilla, Atlantico, Colombia
Hadassah Ein Kerem Medical Center ( Site 1501)
🇮🇱Jerusalem, Israel
CHU Hotel Dieu Nantes ( Site 1101)
🇫🇷Nantes, Pays-de-la-Loire, France
IC La Serena Research ( Site 0410)
🇨🇱La Serena, Coquimbo, Chile
AULSS8 Berica-Ospedale S.Bortolo ( Site 1607)
🇮🇹Vicenza, Veneto, Italy
Oncologos del Occidente S.A. ( Site 0525)
🇨🇴Pereira, Risaralda, Colombia
Queen Mary Hospital ( Site 2501)
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital ( Site 2503)
🇭🇰Hong Kong, Hong Kong