Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)
- Conditions
- Gastric NeoplasmsGastroesophageal Junction Adenocarcinoma
- Interventions
- Registration Number
- NCT03615326
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The study will compare the efficacy and safety of pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer. The primary hypotheses of the study are that pembrolizumab plus trastuzumab in combination with chemotherapy is superior to trastuzumab plus chemotherapy in terms of 1) progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), and 2) overall survival (OS).
- Detailed Description
Pembrolizumab (200 mg) or placebo will be administered intravenously \[IV\] on day 1 of each 3-week cycle. Trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) will be administered IV on day 1 of each 3-week cycle. SOC chemotherapy for the global cohort will either be FP (80 mg/m\^2 cisplatin administered IV on Day 1 of each 3-week cycle and 800 mg/m\^2 5-fluorouracil \[5-FU\] administered IV on Days 1-5 of each 3-week cycle) or CAPOX (1000 mg/m\^2 capecitabine administered orally twice daily \[BID\] on days 1-14 of each 3-week cycle and 130 mg/m\^2 oxaliplatin administered IV on Day 1 of each 3-week cycle). A Japan cohort will receive SOX chemotherapy consisting of S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine \[CDHP\], and potassium oxonate \[Oxo\]) administered orally BID according to Body Surface Area (BSA) on Days 1-14 of each 3-week cycle and oxaliplatin (130 mg/m\^2) administered IV on Day 1 each 3-week cycle.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 738
Inclusion criteria include, but are not limited to:
- Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
- HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor
- Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the site investigator
- Male participants must agree to use approved contraception
- Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception
- 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 trial treatment
- Has a life expectancy of greater than 6 months
- Has adequate organ function
Exclusion criteria include, but are not limited to:
- Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer
- Has had major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
- 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 active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
- Has an active infection requiring systemic therapy
- Has poorly controlled diarrhea
- Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic drugs for other reasons, it is acceptable
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has peripheral neuropathy > Grade 1
- Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
- A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation
- Has active or clinically significant cardiac disease
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products
- Has had an allogeneic tissue/solid organ transplant
- 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 co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, Cluster of Differentiation 137 [CD137])
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Global Pembrolizumab + Standard of Care First Course Pembrolizumab Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Pembrolizumab + Standard of Care First Course Cisplatin Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Pembrolizumab + Standard of Care First Course 5-FU Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Pembrolizumab + Standard of Care First Course Oxaliplatin Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Pembrolizumab + Standard of Care First Course Capecitabine Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Pembrolizumab + Standard of Care First Course Trastuzumab Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Standard of Care Placebo Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Standard of Care Cisplatin Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Standard of Care 5-FU Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Standard of Care Oxaliplatin Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Standard of Care Capecitabine Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Global Standard of Care Trastuzumab Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy. Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin Pembrolizumab Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy. Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin Oxaliplatin Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy. Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin S-1 Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy. Japan Pembrolizumab + Trastuzumab + S-1 Plus Oxaliplatin Trastuzumab Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy. Japan Trastuzumab + S-1 Plus Oxaliplatin Placebo Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy. Japan Trastuzumab + S-1 Plus Oxaliplatin Oxaliplatin Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy. Japan Trastuzumab + S-1 Plus Oxaliplatin S-1 Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy. Japan Trastuzumab + S-1 Plus Oxaliplatin Trastuzumab Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with SOX chemotherapy.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to 63 months OS is defined as the time from randomization to death due to any cause. OS was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.
Progression Free Survival (PFS) Per RECIST 1.1 Assessed by BICR Up to 46 months PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. 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 progression. PFS was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Per RECIST 1.1 Assessed by BICR Up to 63 months ORR is defined as the percentage of participants who have a Complete Response (\[CR\], disappearance of all evidence of disease) or Partial Response (\[PR\], regression of measurable disease and no new sites) per RECIST 1.1 as assessed by blinded independent central review (BICR). ORR was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.
Duration of Response (DOR) Per RECIST 1.1 Assessed by BICR Up to 63 months For participants who demonstrate CR or PR, DOR is defined as the time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first. DOR was determined for first course pembrolizumab in the Global Cohort. Per statistical analysis plan, participants in the Japan-specific SOX Cohort were not included in the efficacy analysis.
Number of Participants Who Experienced an Adverse Event (AE) Up to 63 months An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced an AE is reported for each treatment arm. Per statistical analysis plan, data from the second course of pembrolizumab was not included in the safety analysis.
Number of Participants Who Discontinued Study Treatment Due to AEs Up to 63 months An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued study treatment due to an AE is reported for each treatment arm. Per statistical analysis plan, data from the second course of pembrolizumab was not included in the safety analysis.
Trial Locations
- Locations (192)
Hospital Universitario Central de Asturias ( Site 1402)
🇪🇸Oviedo, Asturias, Spain
Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0025)
🇺🇸Philadelphia, Pennsylvania, United States
University of Rochester ( Site 0041)
🇺🇸Rochester, New York, United States
Sanford Hematology Oncology-Sioux Falls SD ( Site 0004)
🇺🇸Sioux Falls, South Dakota, United States
Memorial Sloan-Kettering Cancer Center ( Site 0017)
🇺🇸New York, New York, United States
IBCC - Instituto Brasileiro de Controle do Cancer ( Site 0204)
🇧🇷Sao Paulo, Brazil
Duke Cancer Institute ( Site 0042)
🇺🇸Durham, North Carolina, United States
University of Miami Sylvester Comprehensive Cancer Center - Plantation ( Site 0026)
🇺🇸Miami, Florida, United States
Allegheny General Hospital ( Site 0053)
🇺🇸Pittsburgh, Pennsylvania, United States
Washington University School of Medicine ( Site 0040)
🇺🇸Saint Louis, Missouri, United States
Southeastern Regional Medical Center, Inc. ( Site 0058)
🇺🇸Newnan, Georgia, United States
Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 0065)
🇺🇸Harrison, New York, United States
Beth Israel Deaconess Medical Center ( Site 0070)
🇺🇸Boston, Massachusetts, United States
Levine Cancer Institute ( Site 0015)
🇺🇸Charlotte, North Carolina, United States
Pacific Cancer Care ( Site 0063)
🇺🇸Monterey, California, United States
Midwestern Regional Medical Center, Inc. ( Site 0059)
🇺🇸Zion, Illinois, United States
Southern Medical Day Care Centre ( Site 2207)
🇦🇺Wollongong, New South Wales, Australia
Monash Health ( Site 2202)
🇦🇺Clayton, Victoria, Australia
CTCA Southwestern ( Site 0060)
🇺🇸Tulsa, Oklahoma, United States
Instituto do Cancer do Ceara ( Site 0208)
🇧🇷Fortaleza, Ceara, Brazil
Centro Investigación del Cáncer James Lind ( Site 0300)
🇨🇱Temuco, Araucania, Chile
Centro Regional de Sub Especialidades Medicas SA ( Site 0502)
🇬🇹Quetzaltenango, Guatemala
Liverpool Hospital ( Site 2206)
🇦🇺Liverpool, New South Wales, Australia
Beijing Cancer Hospital ( Site 2413)
🇨🇳Beijing, Beijing, China
Centre Leon Berard ( Site 0904)
🇫🇷Lyon, Rhone, France
Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 8000)
🇺🇸Roanoke, Virginia, United States
CHU de Rouen ( Site 0912)
🇫🇷Rouen, Ain, France
Westmead Hospital ( Site 2200)
🇦🇺Westmead, New South Wales, Australia
Universitaetsklinikum Carl Gustav Carus der Technischen Univ ( Site 1001)
🇩🇪Dresden, Sachsen, Germany
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0201)
🇧🇷Rio de Janeiro, Brazil
Universitaetsklinikum Leipzig AOeR ( Site 1007)
🇩🇪Leipzig, Sachsen, Germany
SLK-Kliniken Heilbronn ( Site 1015)
🇩🇪Heilbronn, Baden-Wurttemberg, Germany
CHU Hopital Saint Antoine ( Site 0905)
🇫🇷Paris, France
Celan SA ( Site 0504)
🇬🇹Guatemala, Guatemala
Medi-K Cayala ( Site 0505)
🇬🇹Guatemala, Guatemala
900 Hospital of the Joint ( Site 2420)
🇨🇳Fuzhou, Fujian, China
C.H.R.U. de Brest - Hopital Morvan ( Site 0913)
🇫🇷Brest, Finistere, France
Instituto Nacional del Cancer ( Site 0303)
🇨🇱Santiago, Region M. De Santiago, Chile
Auckland City Hospital ( Site 2300)
🇳🇿Auckland, New Zealand
Facharztzentrum Eppendorf ( Site 1025)
🇩🇪Hamburg, Germany
Klinikum Ludwigsburg ( Site 1014)
🇩🇪Ludwigsburg, Baden-Wurttemberg, Germany
Klinikum rechts der Isar der Technischen Universitaet ( Site 1027)
🇩🇪Muenchen, Bayern, Germany
Medizinische Hochschule Hannover ( Site 1019)
🇩🇪Hannover, Niedersachsen, Germany
Kyorin University Hospital ( Site 2608)
🇯🇵Mitaka, Tokyo, Japan
Kumamoto University Hospital ( Site 2601)
🇯🇵Kumamoto, Japan
Hospital Universitario Quiron Madrid ( Site 1407)
🇪🇸Pozuelo de Alarcon, Madrid, Spain
National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 26
🇯🇵Osaka, Japan
Hospital Universitario Marques de Valdecilla ( Site 1405)
🇪🇸Santander, Cantabria, Spain
Severance Hospital Yonsei University Health System ( Site 2700)
🇰🇷Seoul, Korea, Republic of
Asan Medical Center ( Site 2702)
🇰🇷Seoul, Korea, Republic of
Shizuoka Cancer Center Hospital and Research Institute ( Site 2607)
🇯🇵Sunto-gun, Shizuoka, Japan
Tochigi Cancer Center ( Site 2627)
🇯🇵Utsunomiya, Tochigi, Japan
Hospital Universitario Ramon y Cajal ( Site 1400)
🇪🇸Madrid, Spain
Mount Vernon Cancer Centre ( Site 1507)
🇬🇧Northwood, United Kingdom
Manor Hospital Walsall England ( Site 1515)
🇬🇧Walsall, United Kingdom
Seoul National University Hospital ( Site 2703)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 2701)
🇰🇷Seoul, Korea, Republic of
Przychodnia Lekarska Komed ( Site 1716)
🇵🇱Konin, Wielkopolskie, Poland
University College London Hospital NHS Foundation Trust ( Site 1508)
🇬🇧London, London, City Of, United Kingdom
The Christie Hospital NHS Foundation Trust ( Site 1503)
🇬🇧Manchester, United Kingdom
University of Texas MD Anderson Cancer Center ( Site 0001)
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance ( Site 0038)
🇺🇸Seattle, Washington, United States
UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0045)
🇺🇸Los Angeles, California, United States
UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0050)
🇺🇸Orange, California, United States
Dana-Farber Cancer Institute [Boston, MA] ( Site 0010)
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0071)
🇺🇸Middletown, New Jersey, United States
Minnesota Oncology Hematology, PA ( Site 8001)
🇺🇸Minneapolis, Minnesota, United States
CIONC - Centro Integrado de Oncologia de Curitiba ( Site 0205)
🇧🇷Curitiba, Parana, Brazil
Pontificia Universidad Catolica de Chile ( Site 0301)
🇨🇱Santiago, Region M. De Santiago, Chile
Fujian Provincial Cancer Hospital ( Site 2418)
🇨🇳Fuzhou, Fujian, China
The First Affiliated Hospital of Xiamen University ( Site 2431)
🇨🇳Xiamen, Fujian, China
HUS Hopital Hautepierre ( Site 0910)
🇫🇷Strasbourg, Bas-Rhin, France
Innere Medizin I, Universitaetsklinikum Tuebingen ( Site 1020)
🇩🇪Tuebingen, Baden-Wurttemberg, Germany
Charite-Universitaetsmedizin Berlin Campus Virchow-Klinikum ( Site 1026)
🇩🇪Berlin, Germany
Klinikum Bremen Nord ( Site 1017)
🇩🇪Bremen, Germany
Rabin Medical Center ( Site 1602)
🇮🇱Petah Tikva, Israel
Gunma Prefectural Cancer Center ( Site 2602)
🇯🇵Ohta, Gunma, Japan
Hyogo Cancer Center ( Site 2619)
🇯🇵Akashi, Hyogo, Japan
Aichi Cancer Center Hospital ( Site 2617)
🇯🇵Nagoya, Aichi, Japan
Kanagawa Cancer Center ( Site 2603)
🇯🇵Yokohama, Kanagawa, Japan
Hiroshima City Hiroshima Citizens Hospital ( Site 2625)
🇯🇵Hiroshima, Japan
Niigata Cancer Center Hospital ( Site 2622)
🇯🇵Niigata, Japan
Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 1708)
🇵🇱Koscierzyna, Pomorskie, Poland
Uniwersytecki Szpital Kliniczny im. J. M. Radeckiego we Wroclawiu ( Site 1705)
🇵🇱Wroclaw, Dolnoslaskie, Poland
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1815)
🇷🇺Chelyabinsk, Chelyabinskaya Oblast, Russian Federation
Blokhin National Medical Oncology ( Site 1805)
🇷🇺Moscow, Moskva, Russian Federation
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1801)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Hospital General Universitari Vall d Hebron ( Site 1401)
🇪🇸Barcelona, Spain
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2001)
🇹🇷Istanbul, Turkey
Medical Center Asklepion LLC ( Site 2115)
🇺🇦Khodosivka, Kyivska Oblast, Ukraine
Medical Centre LLC Oncolife ( Site 2103)
🇺🇦Zaporizhzhya, Zaporizka Oblast, Ukraine
Ninewells Hospital and Medical School ( Site 1504)
🇬🇧Dundee, Dundee City, United Kingdom
Castle Hill Hospital ( Site 1501)
🇬🇧Cottingham, East Riding Of Yorkshire, United Kingdom
Shanghai General Hospital ( Site 2404)
🇨🇳Shanghai, Anhui, China
Peking Union Medical College Hospital ( Site 2419)
🇨🇳Beijing, Beijing, China
Fifth Medical Center of CPLA General Hospital ( Site 2415)
🇨🇳Beijing, Beijing, China
Guangdong General Hospital ( Site 2433)
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital ( Site 2407)
🇨🇳Harbin, Heilongjiang, China
Henan Cancer Hospital ( Site 2400)
🇨🇳Zhengzhou, Henan, China
Xiangya Hospital Central-South University ( Site 2426)
🇨🇳Changsha, Hunan, China
Jiangsu Cancer Hospital ( Site 2432)
🇨🇳Nanjing, Jiangsu, China
The First Hospital Of Jilin University ( Site 2402)
🇨🇳Chang chun, Jilin, China
Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2430)
🇨🇳Urumqi, Xinjiang, China
Fudan University Shanghai Cancer Center ( Site 2424)
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital ( Site 2409)
🇨🇳Hangzhou, Zhejiang, China
Hospital de Caridade de Ijui ( Site 0202)
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Hospital Nossa Senhora da Conceicao ( Site 0203)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Clinica Universidad Catolica del Maule ( Site 0305)
🇨🇱Talca, Maule, Chile
Hospital Sao Rafael ( Site 0209)
🇧🇷Salvador, Bahia, Brazil
AUOP Ospedale Santa Chiara ( Site 1100)
🇮🇹Pisa, Toscana, Italy
Humanitas Gavazzeni ( Site 1106)
🇮🇹Bergamo, Italy
Universita Magna Graecia di Catanzaro ( Site 1107)
🇮🇹Catanzaro, Italy
IEO Istituto Europeo di Oncologia ( Site 1105)
🇮🇹Milano, Italy
Azienda Ospedaliero - Universitaria Policlinico di Modena ( Site 1102)
🇮🇹Modena, Italy
A.O.U. Universita degli Studi della Campania-Luigi Vanvitelli ( Site 1103)
🇮🇹Napoli, Italy
Istituto Oncologico Veneto ( Site 1101)
🇮🇹Padova, Italy
Ospedale Civile Spirito Santo ( Site 1104)
🇮🇹Pescara, Italy
St Georges University Hospitals NHS Foundation Trust. ( Site 1500)
🇬🇧London, London, City Of, United Kingdom
Royal Marsden NHS Foundation Trust ( Site 1512)
🇬🇧London, United Kingdom
Asklepios Klinik Altona ( Site 1000)
🇩🇪Hamburg, Germany
Rambam Health Care Campus ( Site 1606)
🇮🇱Haifa, Israel
National Cancer Center Hospital East ( Site 2605)
🇯🇵Kashiwa, Chiba, Japan
Osaki Citizen Hospital ( Site 2626)
🇯🇵Osaki, Miyagi, Japan
National Hospital Organization Kyushu Cancer Center ( Site 2609)
🇯🇵Fukuoka, Japan
Toranomon Hospital ( Site 2628)
🇯🇵Tokyo, Japan
Tokyo Metropolitan Komagome Hospital ( Site 2606)
🇯🇵Tokyo, Japan
Osaka International Cancer Institute ( Site 2613)
🇯🇵Osaka, Japan
National Cancer Center Hospital ( Site 2612)
🇯🇵Tokyo, Japan
Tallaght University Hospital ( Site 1513)
🇮🇪Dublin, Ireland
CEPON - Centro de Pesquisas Oncologicas ( Site 0200)
🇧🇷Florianopolis, Santa Catarina, Brazil
Fundacion Arturo Lopez Perez FALP ( Site 0302)
🇨🇱Santiago, Region M. De Santiago, Chile
Centre Oscar Lambret ( Site 0911)
🇫🇷Lille, Nord, France
Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0902)
🇫🇷Saint-Herblain, Val-de-Marne, France
Hadassah Ein Kerem Medical Center ( Site 1604)
🇮🇱Jerusalem, Israel
Saint James's Hospital ( Site 1505)
🇮🇪Dublin, Ireland
Soroka University Medical Center ( Site 1603)
🇮🇱Beer Sheva, Israel
Edith Wolfson Medical Center ( Site 1605)
🇮🇱Holon, Israel
Sourasky Medical Center ( Site 1601)
🇮🇱Tel Aviv, Israel
Grupo Angeles SA ( Site 0501)
🇬🇹Guatemala, Guatemala
Meir Medical Center ( Site 1609)
🇮🇱Kfar-Saba, Israel
Chaim Sheba Medical Center. ( Site 1607)
🇮🇱Ramat Gan, Israel
National Hospital Organization Shikoku Cancer Center ( Site 2615)
🇯🇵Matsuyama, Ehime, Japan
Chiba Cancer Center ( Site 2623)
🇯🇵Chiba, Japan
Gifu University Hospital ( Site 2621)
🇯🇵Gifu, Japan
Osaka General Medical Center ( Site 2624)
🇯🇵Osaka, Japan
The Cancer Institute Hospital of JFCR ( Site 2610)
🇯🇵Tokyo, Japan
Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 1709)
🇵🇱Lublin, Lubelskie, Poland
Hopital Jean Minjoz Besancon ( Site 0901)
🇫🇷Besancon, Doubs, France
Institut Gustave Roussy ( Site 0900)
🇫🇷Villejuif, Val-de-Marne, France
Oncomedica ( Site 0500)
🇬🇹Guatemala, Guatemala
Nucare Center ( Site 0506)
🇬🇹Guatemala, Guatemala
Beaumont Hospital ( Site 1506)
🇮🇪Dublin, Ireland
Kobe City Medical Center General Hospital ( Site 2614)
🇯🇵Kobe, Hyogo, Japan
Ibaraki Prefectural Central Hospital ( Site 2611)
🇯🇵Kasama, Ibaraki, Japan
Kagawa University Hospital ( Site 2604)
🇯🇵Kita-gun, Kagawa, Japan
Kansai Medical University Hospital ( Site 2618)
🇯🇵Hirakata, Osaka, Japan
Kindai University Hospital ( Site 2616)
🇯🇵Osakasayama, Osaka, Japan
Osaka University Hospital ( Site 2600)
🇯🇵Suita, Osaka, Japan
Saitama Cancer Center ( Site 2620)
🇯🇵Kitaadachi-gun, Saitama, Japan
Podolsky City Clinical Hospital ( Site 1817)
🇷🇺Podolsk, Moskovskaya Oblast, Russian Federation
Leningrad Regional Oncology Center ( Site 1800)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
Royal Hospital in Derby ( Site 1514)
🇬🇧Derby, Derbyshire, United Kingdom
Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2106)
🇺🇦Lviv, Lvivska Oblast, Ukraine
Dolnoslaskie Centrum Onkologii. ( Site 1712)
🇵🇱Wroclaw, Dolnoslaskie, Poland
Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1715)
🇵🇱Gdynia, Pomorskie, Poland
Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2000)
🇹🇷Erzurum, Turkey
Dokuz Eylul Universitesi Tip Fakultesi Hastanesi ( Site 2011)
🇹🇷Izmir, Turkey
Sakarya Universitesi Egitim ve Arastirma Hastanesi ( Site 2012)
🇹🇷Sakarya, Turkey
Kyiv City Clinical Oncology Centre ( Site 2110)
🇺🇦Kyiv, Ukraine
MI Odessa Regional Oncological Centre ( Site 2108)
🇺🇦Odesa, Odeska Oblast, Ukraine
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
🇵🇱Warszawa, Mazowieckie, Poland
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1807)
🇷🇺Ufa, Baskortostan, Respublika, Russian Federation
St Petersburg City Clinical Oncology Dispensary ( Site 1812)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Hospital General Universitario de Elche ( Site 1404)
🇪🇸Elche, Alicante, Spain
Abdurrahman Yurtaslan Onkoloji Egitim ve Arastirma Hastanesi ( Site 2006)
🇹🇷Ankara, Turkey
Trakya Universitesi Tip Fakultesi ( Site 2015)
🇹🇷Edirne, Turkey
MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2101)
🇺🇦Kryviy Rih, Dnipropetrovska Oblast, Ukraine
Royal Marsden Hospital ( Site 1510)
🇬🇧Sutton, Surrey, United Kingdom
City Clinical Hosp.4 of DCC ( Site 2102)
🇺🇦Dnipro, Dnipropetrovska Oblast, Ukraine
Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1710)
🇵🇱Bielsko-Biala, Slaskie, Poland
Medical University REAVIZ ( Site 1816)
🇷🇺Samara, Samarskaya Oblast, Russian Federation
Adana Sehir Hastanesi ( Site 2002)
🇹🇷Adana, Turkey
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 2017)
🇹🇷Ankara, Turkey
Malatya Inonu Universitesi Tip Fakultesi Hastanesi ( Site 2009)
🇹🇷Malatya, Turkey
Clinic of National Cancer Institute ( Site 2104)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
MI Precarpathian Clinical Oncology Center ( Site 2105)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 2114)
🇺🇦Kyiv, Kyivska Oblast, Ukraine
Zhongshan Hospital affiliated to Fudan University ( Site 2401)
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital.Zhejiang University ( Site 2408)
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital ( Site 2412)
🇨🇳Hangzhou, Zhejiang, China
Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1410)
🇪🇸Badalona, Barcelona, Spain
Communal non profit enterprise Regional Clinical Oncology Center ( Site 2112)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine