Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma (HCC) and Complete Radiological Response After Surgical Resection or Local Ablation (MK-3475-937 / KEYNOTE-937)

Phase 3

Active, not recruiting

• Conditions: Hepatocellular Carcinoma
• Interventions: Biological: Pembrolizumab; Drug: Placebo

• Registration Number: NCT03867084
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This study will evaluate the safety and efficacy of pembrolizumab (MK-3475) versus placebo as adjuvant therapy in participants with hepatocellular carcinoma (HCC) and complete radiological response after surgical resection or local ablation. The primary hypotheses of this study are that adjuvant pembrolizumab is superior to placebo with respect to: 1) recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and 2) overall survival (OS).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-06
• Study First Submitted QC: 2019-03-06
• Study First Posted: 2019-03-07
• Study Start: 2019-05-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-12
• Last Update Posted: 2024-11-14
• Primary Completion: 2027-10-31
• Study Completion: 2029-08-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 950

Inclusion Criteria

• Has a diagnosis of HCC by radiological criteria and/or pathological confirmation.
• Has an eligibility scan (CT of the chest, triphasic CT scan or MRI of the abdomen, and CT or MRI of the pelvis) confirming complete radiological response ≥4 weeks after complete surgical resection or local ablation. Randomization needs to occur within 12 weeks of the date of surgical resection or local ablation.
• Has no radiologic evidence of disease prior to enrollment.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to Cycle 1, Day 1.
• Has a Child-Pugh class A liver score (5 to 6 points) within 7 days prior to Cycle 1, Day 1.
• Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 days prior to Cycle 1, Day 1.
• Has controlled hepatitis B (Hep B).
• Has recovered adequately from toxicity and/or complications from the local intervention (surgical resection or local ablation) prior to starting study treatment.
• If female, is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); or 2) Is a WOCBP and using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (a WOCBP must have a negative pregnancy test within 72 hours before the first dose of study treatment).
• If undergoing surgical resection, has submitted a tumor tissue sample during Screening.
• Has adequate organ function.

Exclusion Criteria

• Has a known additional malignancy that is progressing or has required active antineoplastic treatment (including hormonal) or surgery within the past 3 years.
• Has had esophageal or gastric variceal bleeding within the last 6 months.
• Has clinically apparent ascites on physical examination.
• Has had clinically diagnosed hepatic encephalopathy in the last 6 months.
• Has received local therapy to liver ablation other than with radiofrequency or microwave ablation.
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has dual active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection at study entry.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active tuberculosis (TB; Bacillus tuberculosis).
• 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 (eg, CTLA-4, OX-40, CD137).
• Has received prior systemic anti-cancer therapy for HCC including investigational agents.
• Is receiving any of the following prohibited concomitant therapies:1) Antineoplastic systemic chemotherapy or biological therapy; 2) Immunotherapy not specified in this protocol; 3) Investigational agents other than pembrolizumab; 4) Radiation therapy; 5) Oncological surgical therapy; or systemic glucocorticoids for any purpose other than to modulate symptoms from an AE that is suspected to have an immunologic etiology.
• Has received a live vaccine within 30 days prior to the first dose of study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to Cycle 1, Day 1.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1, Day 1.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• Has had an allogenic tissue/solid organ transplant.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab	Pembrolizumab	Participants receive intravenous (IV) pembrolizumab at 200 mg on Day 1 of each 21-day cycle for up to 17 cycles.
Placebo	Placebo	Participants receive IV placebo on Day 1 of each 21-day cycle for up to 17 cycles.

Primary Outcome Measures

Name	Time	Method
Recurrence-Free Survival (RFS)	Up to ~6 years	RFS is defined as the time from randomization to first documentation of disease recurrence (local, regional, or distant) as assessed by BICR or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death), whichever occurs first.
Overall Survival (OS)	Up to ~8 years	OS is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants who Experience an Adverse Event (AE)	Up to ~8 years	An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
Percentage of Participants who Discontinue Study Treatment Due to an AE	Up to ~1 year	An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status (GHS) / Quality of Life (QoL) Scale Score	Baseline and time of last patient reported outcome (PRO) assessment (up to ~5 years)	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients, including a combined GHS/QoL (Items 29 and 30) scale. Per protocol, the change from baseline in the combined GHS/QoL score (range: 0-100) will be reported. Higher overall GHS/QoL scores indicate higher GHS/QoL.
Change from Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Scale Score	Baseline and time of last PRO assessment (up to ~5 years)	The EORTC QLQ-HCC18 is an HCC-specific questionnaire, administered in addition to the EORTC QLQ-C30, with scores ranging from 0-100. Higher scores indicate more severe symptoms/problems. Change from baseline in the EORTC QLQ-HCC18 scale score will be reported.
Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score	Baseline and time of last PRO assessment (up to ~5 years)	The EQ-5D-5L measured health-related outcomes, assessing 5 health state dimensions (mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression) on a 5-point scale from 1 (no problem) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health.

Trial Locations

Locations (249)

UZ Leuven ( Site 0377); 🇧🇪 Leuven, Vlaams-Brabant, Belgium

City of Hope Medical Center ( Site 0027); 🇺🇸 Duarte, California, United States

Fundación favaloro para la Docencia e Investigación Médica ( Site 0808); 🇦🇷 Buenos Aires, Caba, Argentina

The University of Arizona Cancer Center - North Campus ( Site 0039); 🇺🇸 Tucson, Arizona, United States

University Medical Center New Orleans ( Site 0014); 🇺🇸 New Orleans, Louisiana, United States

Hospital Britanico de Buenos Aires ( Site 0792); 🇦🇷 Buenos Aires, Argentina

University of Massachusetts Worcester ( Site 0017); 🇺🇸 Worcester, Massachusetts, United States

Krankenhaus Nord-West GmbH ( Site 0472); 🇩🇪 Frankfurt am Main, Hessen, Germany

Hospital Universitario Austral ( Site 0795); 🇦🇷 Pilar, Buenos Aires, Argentina

Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0826); 🇧🇷 Sao Paulo, Brazil

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0211); 🇨🇦 Montreal, Quebec, Canada

Universitaetsklinikum Frankfurt ( Site 0467); 🇩🇪 Frankfurt, Hessen, Germany

Baylor Scott & White Medical Center - Temple ( Site 0089); 🇺🇸 Temple, Texas, United States

Universitatsklinikum Carl Gustav Carus ( Site 0459); 🇩🇪 Dresden, Sachsen, Germany

Hospital Paulistano ( Site 0829); 🇧🇷 São Paulo, Sao Paulo, Brazil

Erasme Hospital ( Site 0376); 🇧🇪 Bruxelles, Bruxelles-Capitale, Region De, Belgium

University of New Mexico ( Site 0041); 🇺🇸 Albuquerque, New Mexico, United States

Alfred Health ( Site 0230); 🇦🇺 Melbourne, Victoria, Australia

Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0802); 🇦🇷 Santa Fe, Argentina

Instituto COI de Pesquisa Educacao e Gestao ( Site 0825); 🇧🇷 Rio de Janeiro, Brazil

University of Iowa ( Site 0067); 🇺🇸 Iowa City, Iowa, United States

Princess Alexandra Hospital ( Site 0228); 🇦🇺 Woollongabba, Queensland, Australia

Hospital Aleman ( Site 0806); 🇦🇷 Buenos Aires, Argentina

Monash Health ( Site 0233); 🇦🇺 Clayton, Victoria, Australia

Hospital Italiano ( Site 0793); 🇦🇷 Buenos Aires, Argentina

Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0820); 🇧🇷 Itajai, Santa Catarina, Brazil

Beijing Cancer Hospital ( Site 0155); 🇨🇳 Beijing, Beijing, China

UZ Gent ( Site 0375); 🇧🇪 Gent, Oost-Vlaanderen, Belgium

Hopital de la Timone ( Site 0442); 🇫🇷 Marseille, Bouches-du-Rhone, France

CIONC - Centro Integrado de Oncologia de Curitiba ( Site 0813); 🇧🇷 Curitiba, Parana, Brazil

Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0828); 🇧🇷 Sao Paulo, Brazil

A.C. Camargo Cancer Center ( Site 0827); 🇧🇷 Sao Paulo, Brazil

Casa de Saude Santa Marcelina ( Site 0821); 🇧🇷 Sao Paulo, Brazil

Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 0550); 🇮🇹 Milano, Italy

Istituto Tumori Giovanni Paolo II ( Site 0543); 🇮🇹 Bari, Italy

Universitaetsklinikum Hamburg-Eppendorf ( Site 0469); 🇩🇪 Hamburg, Germany

Staedtisches Klinikum Dresden ( Site 0471); 🇩🇪 Dresden, Sachsen, Germany

Nova Scotia Health Authority QEII-HSC ( Site 0208); 🇨🇦 Halifax, Nova Scotia, Canada

SLK-Kliniken Heilbronn GmbH ( Site 0460); 🇩🇪 Heilbronn, Baden-Wurttemberg, Germany

Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello ( Site 0547); 🇮🇹 Palermo, Sicilia, Italy

Semmelweis University ( Site 0480); 🇭🇺 Budapest, Hungary

Toranomon Hospital Kajigaya ( Site 0109); 🇯🇵 Kawasaki, Kanagawa, Japan

Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 0484); 🇭🇺 Kaposvár, Somogy, Hungary

CHU Montpellier. ( Site 0443); 🇫🇷 Montpellier, Herault, France

Rambam Medical Center ( Site 0524); 🇮🇱 Haifa, Israel

Sourasky Medical Center ( Site 0522); 🇮🇱 Tel Aviv, Israel

Hopital Paul Brousse ( Site 0447); 🇫🇷 Villejuif, Val-de-Marne, France

Ehime University Hospital ( Site 0123); 🇯🇵 Toon, Ehime, Japan

Medizinische Hochschule Hannover ( Site 0458); 🇩🇪 Hannover, Niedersachsen, Germany

Universitaetsklinikum Koeln ( Site 0463); 🇩🇪 Koeln, Nordrhein-Westfalen, Germany

SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0482); 🇭🇺 Szeged, Csongrad, Hungary

Kurume University Hospital ( Site 0119); 🇯🇵 Kurume, Fukuoka, Japan

Kagawa Prefectural Central Hospital ( Site 0122); 🇯🇵 Takamatsu, Kagawa, Japan

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0540); 🇮🇹 Milano, Italy

Haddassah Medical Organization - Ein Kerem ( Site 0519); 🇮🇱 Jerusalem, Israel

Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0102); 🇯🇵 Sapporo, Hokkaido, Japan

Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 0483); 🇭🇺 Kecskemét, Bacs-Kiskun, Hungary

Gulhane Egitim ve Arastirma Hastanesi ( Site 0741); 🇹🇷 Ankara, Turkey

Tallaght University Hospital ( Site 0499); 🇮🇪 Dublin, Ireland

Yokohama City University Medical Center ( Site 0110); 🇯🇵 Yokohama, Kanagawa, Japan

Kagawa University Hospital ( Site 0121); 🇯🇵 Kita-gun, Kagawa, Japan

Rabin Medical Center ( Site 0520); 🇮🇱 Petah Tikva, Israel

Kanazawa University Hospital ( Site 0111); 🇯🇵 Kanazawa, Ishikawa, Japan

University Hospital, Kyoto Prefectural University of Medicine ( Site 0112); 🇯🇵 Kyoto, Japan

Toranomon Hospital ( Site 0108); 🇯🇵 Tokyo, Japan

Seoul National University Bundang Hospital ( Site 0313); 🇰🇷 Seongnam-si, Kyonggi-do, Korea, Republic of

ID Clinic ( Site 0619); 🇵🇱 Myslowice, Slaskie, Poland

University Hospital Coventry and Warwickshire NHS Trust ( Site 0754); 🇬🇧 Coventry, United Kingdom

Namik Kemal Universitesi Tip Fakultesi ( Site 0738); 🇹🇷 Tekirdag, Tekirdas, Turkey

Universal Clinic Oberig-Oncology Center ( Site 0786); 🇺🇦 Kyiv, Ukraine

Kings College Hospital NHS Foundation Trust ( Site 0758); 🇬🇧 London, London, City Of, United Kingdom

Leeds Teaching Hospitals NHS Trust ( Site 0751); 🇬🇧 Leeds, United Kingdom

Acıbadem Maslak Hastanesi ( Site 0742); 🇹🇷 Istanbul, Turkey

Medical Center Dobrobut Clinic ( Site 0785); 🇺🇦 Kyiv, Ukraine

Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0730); 🇹🇷 Istanbul, Turkey

Dokuz Eylul Universitesi ( Site 0740); 🇹🇷 Izmir, Turkey

Nottingham University Hospitals NHS Trust ( Site 0756); 🇬🇧 Nottingham, United Kingdom

The Beatson West of Scotland Cancer Centre ( Site 0750); 🇬🇧 Glasgow, Glasgow City, United Kingdom

Banner MD Anderson Cancer Center ( Site 0026); 🇺🇸 Gilbert, Arizona, United States

Regional Cancer Center ( Site 0054); 🇺🇸 Fort Myers, Florida, United States

Royal Prince Alfred Hospital AW ( Site 0225); 🇦🇺 Camperdown, New South Wales, Australia

Royal Adelaide Hospital ( Site 0234); 🇦🇺 Adelaide, South Australia, Australia

St Vincents Hospital Melbourne ( Site 0227); 🇦🇺 Fitzroy, Victoria, Australia

Royal Perth Hospital ( Site 0229); 🇦🇺 Perth, Western Australia, Australia

Hospital de Clinicas de Porto Alegre ( Site 0824); 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

University Hospital Basel ( Site 0709); 🇨🇭 Basel, Basel-Stadt, Switzerland

Cancer Hospital Chinese Academy of Medical Sciences ( Site 0156); 🇨🇳 Beijing, Beijing, China

Guangdong General Hospital ( Site 0166); 🇨🇳 Guangzhou, Guangdong, China

Wuhan Union Hospital ( Site 0173); 🇨🇳 Wuhan, Hubei, China

Fujian Provincial Cancer Hospital ( Site 0165); 🇨🇳 Fuzhou, Fujian, China

900 Hospital of the Joint ( Site 0197); 🇨🇳 Fuzhou, Fujian, China

Hunan Cancer Hospital ( Site 0168); 🇨🇳 Changsha, Hunan, China

Fudan University Shanghai Cancer Center ( Site 0161); 🇨🇳 Shanghai, Shanghai, China

Zhongshan Hospital Fudan University ( Site 0193); 🇨🇳 Shanghai, Shanghai, China

Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0174); 🇨🇳 Shanghai, Shanghai, China

Zhongshan Hospital affiliated to Fudan University ( Site 0153); 🇨🇳 Shanghai, Shanghai, China

West China Hospital of Sichuan University ( Site 0162); 🇨🇳 Chengdu, Sichuan, China

Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0157); 🇨🇳 Urumqi, Xinjiang, China

The First Affiliated Hospital of Xi an Jiaotong University ( Site 0164); 🇨🇳 XI An, Shanxi, China

Zhejiang Cancer Hospital ( Site 0171); 🇨🇳 Hangzhou, Zhejiang, China

Herlev Hospital ( Site 0421); 🇩🇰 Herlev, Hovedstaden, Denmark

Aarhus Universitets hospital ( Site 0420); 🇩🇰 Aarhus N, Midtjylland, Denmark

Odense Universitets Hospital ( Site 0422); 🇩🇰 Odense C, Syddanmark, Denmark

Indiana University Simon Cancer Center ( Site 0075); 🇺🇸 Indianapolis, Indiana, United States

University of Cincinnati Medical Center ( Site 0084); 🇺🇸 Cincinnati, Ohio, United States

Stephenson Cancer Center ( Site 0045); 🇺🇸 Oklahoma City, Oklahoma, United States

Massachusetts General Hospital ( Site 0062); 🇺🇸 Boston, Massachusetts, United States

Beth Israel Deaconess Medical Ctr. ( Site 0033); 🇺🇸 Boston, Massachusetts, United States

Henry Ford Hospital-GI/Hepatology Research ( Site 0047); 🇺🇸 Detroit, Michigan, United States

Vanderbilt Ingram Cancer Center ( Site 0006); 🇺🇸 Nashville, Tennessee, United States

Virginia Mason Medical Center ( Site 0028); 🇺🇸 Seattle, Washington, United States

CHU Bordeaux Haut-Leveque ( Site 0437); 🇫🇷 Pessac, Gironde, France

Hopital Beaujon ( Site 0439); 🇫🇷 Clichy, Hauts-de-Seine, France

St Vincent's University Hospital ( Site 0498); 🇮🇪 Dublin, Ireland

A O U Policlinico di Modena ( Site 0548); 🇮🇹 Modena, Abruzzo, Italy

HUS Hopital Hautepierre ( Site 0445); 🇫🇷 Strasbourg, Bas-Rhin, France

Hopital Claude Huriez CHRU LILLE ( Site 0440); 🇫🇷 Lille, Nord, France

Hospital Provincial del Centenario ( Site 0794); 🇦🇷 Rosario, Santa Fe, Argentina

Belfast City Hospital ( Site 0752); 🇬🇧 Belfast, Northern Ireland, United Kingdom

Hospital de Cancer de Pernambuco ( Site 0815); 🇧🇷 Recife, Pernambuco, Brazil

Clinica de Oncologia Reichow ( Site 0818); 🇧🇷 Blumenau, Santa Catarina, Brazil

Kantonsspital Winterthur ( Site 0714); 🇨🇭 Winterthur, Zurich, Switzerland

China Medical University Hospital ( Site 0333); 🇨🇳 Taichung, Taiwan

Institut Kanser Negara - National Cancer Institute ( Site 0294); 🇲🇾 Putrajaya Wilayah Persekutuan, Wilayah Persekutuan Putrajaya, Malaysia

Regional Oncology Center of Kharkiv ( Site 0777); 🇺🇦 Kharkiv, Kharkivska Oblast, Ukraine

Universitaetsspital Zurich ( Site 0713); 🇨🇭 Zurich, Switzerland

Weston Park Hospital ( Site 0753); 🇬🇧 Sheffield, Derbyshire, United Kingdom

MI Odessa Regional Oncological Centre ( Site 0776); 🇺🇦 Odesa, Odeska Oblast, Ukraine

The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0757); 🇬🇧 Birkenhead, Wirral, United Kingdom

Cambridge University Hospitals NHS Trust ( Site 0755); 🇬🇧 Cambridge, Cambridgeshire, United Kingdom

Shalimov s NI of Surgery and Transplantation ( Site 0781); 🇺🇦 Kyiv, Kyivska Oblast, Ukraine

CI City Clinical Hospital # 3 ( Site 0783); 🇺🇦 Zaporizhzhia, Zaporizka Oblast, Ukraine

AOU di Bologna Policliico S. Orsola-Malpighi ( Site 0541); 🇮🇹 Bologna, Italy

Azienda Ospedaliero Universitaria Careggi ( Site 0549); 🇮🇹 Firenze, Italy

Ospedale del Mare ( Site 0545); 🇮🇹 Napoli, Italy

Ankara Sehir Hastanesi ( Site 0731); 🇹🇷 Ankara, Turkey

Kindai University Hospital ( Site 0116); 🇯🇵 Osakasayama, Osaka, Japan

Saga-Ken Medical Centre Koseikan ( Site 0120); 🇯🇵 Saga, Japan

The University of Tokyo Hospital ( Site 0105); 🇯🇵 Tokyo, Japan

Boston Medical Center ( Site 0025); 🇺🇸 Boston, Massachusetts, United States

North Shore-Long Island Jewish Health System ( Site 0068); 🇺🇸 Lake Success, New York, United States

Miami Valley Hospital South ( Site 0093); 🇺🇸 Centerville, Ohio, United States

Liverpool Hospital ( Site 0226); 🇦🇺 Liverpool, New South Wales, Australia

University Hospital Antwerp (UZA) ( Site 0374); 🇧🇪 Edegem, Antwerpen, Belgium

Southern Medical University Nanfang Hospital ( Site 0172); 🇨🇳 Guangzhou, Guangdong, China

Complex Cancer Center Plovdiv-First Medical Oncology Department ( Site 0982); 🇧🇬 Plovdiv, Bulgaria

Peking University People's Hospital ( Site 0191); 🇨🇳 Beijing, Beijing, China

Anhui Provincil Hospital South District ( Site 0181); 🇨🇳 Hefei, Anhui, China

McGill University Health Centre ( Site 0207); 🇨🇦 Montreal, Quebec, Canada

The Third Xiangya Hospital of Central South University ( Site 0167); 🇨🇳 Changsha, Hunan, China

Hunan Provincial People Hospital ( Site 0192); 🇨🇳 Changsha, Hunan, China

Hubei Cancer Hospital ( Site 0189); 🇨🇳 Wuhan, Hubei, China

CHU Rangueil ( Site 0441); 🇫🇷 Toulouse, Haute-Garonne, France

Universitaetsklinikum Wuerzburg ( Site 0468); 🇩🇪 Wuerzburg, Bayern, Germany

Klinikum rechts der Isar der Technischen Universitaet ( Site 0470); 🇩🇪 Muenchen, Bayern, Germany

Universitaetsklinikum Duesseldorf ( Site 0461); 🇩🇪 Duesseldorf, Nordrhein-Westfalen, Germany

Charite - Campus Virchow Klinikum ( Site 0457); 🇩🇪 Berlin, Germany

Universitaetsklinikum Tuebingen ( Site 0466); 🇩🇪 Tuebingen, Baden-Wurttemberg, Germany

Debreceni Egyetem Klinikai Kozpont Onkologiai Tanszek ( Site 0481); 🇭🇺 Debrecen, Hungary

Azienda Ospedaliera Ordine Mauriziano di Torino ( Site 0542); 🇮🇹 Torino, Piemonte, Italy

Chaim Sheba Medical Center ( Site 0523); 🇮🇱 Ramat Gan, Israel

Azienda Ospedaliero Universitaria Pisana ( Site 0546); 🇮🇹 Pisa, Italy

Musashino Red Cross Hospital ( Site 0107); 🇯🇵 Musashino, Tokyo, Japan

Saitama Medical University Hospital ( Site 0104); 🇯🇵 Iruma-gun, Saitama, Japan

Kyorin University Hospital ( Site 0106); 🇯🇵 Mitaka, Tokyo, Japan

Chiba University Hospital ( Site 0103); 🇯🇵 Chiba, Japan

National Hospital Organization Kyushu Medical Center ( Site 0118); 🇯🇵 Fukuoka, Japan

Hiroshima University Hospital ( Site 0117); 🇯🇵 Hiroshima, Japan

Japanese Red Cross Osaka Hospital ( Site 0113); 🇯🇵 Osaka, Japan

Osaka Metropolitan University Hospital. ( Site 0114); 🇯🇵 Osaka, Japan

Severance Hospital Yonsei University Health System ( Site 0309); 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center ( Site 0310); 🇰🇷 Seoul, Korea, Republic of

Wakayama Medical University Hospital ( Site 0115); 🇯🇵 Wakayama, Japan

Samsung Medical Center ( Site 0311); 🇰🇷 Seoul, Korea, Republic of

National Cancer Center ( Site 0314); 🇰🇷 Goyang-si, Kyonggi-do, Korea, Republic of

Seoul National University Hospital ( Site 0312); 🇰🇷 Seoul, Korea, Republic of

The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0315); 🇰🇷 Seoul, Korea, Republic of

Hospital Universiti Sains Malaysia ( Site 0295); 🇲🇾 Kubang Kerian, Kelantan, Malaysia

Penang Adventist Hospital ( Site 0289); 🇲🇾 George Town, Pulau Pinang, Malaysia

Gleneagles Penang ( Site 0290); 🇲🇾 Penang, Pulau Pinang, Malaysia

Sarawak General Hospital ( Site 0293); 🇲🇾 Kuching, Sarawak, Malaysia

University Malaya Medical Centre ( Site 0288); 🇲🇾 Kuala Lumpur, Malaysia

Auckland City Hospital ( Site 0246); 🇳🇿 Auckland, New Zealand

Christchurch Hospital ( Site 0247); 🇳🇿 Christchurch, Canterbury, New Zealand

MTZ Clinical Research Sp. z o. o. ( Site 0608); 🇵🇱 Warsaw, Mazowieckie, Poland

Oslo Universitetssykehus HF. Ulleval ( Site 0433); 🇳🇴 Oslo, Norway

Copernicus PL Sp. z o.o. ( Site 0603); 🇵🇱 Gdansk, Pomorskie, Poland

Izerskie Centrum Pulmonologii i Chemioterapii IZER-MED Spolka z o.o. ( Site 0607); 🇵🇱 Szklarska Poreba, Dolnoslaskie, Poland

Siberian Clinical Center of FMBA ( Site 0918); 🇷🇺 Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation

Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0604); 🇵🇱 Koszalin, Zachodniopomorskie, Poland

Altay Regional Oncology Dispensary ( Site 0919); 🇷🇺 Barnaul, Altayskiy Kray, Russian Federation

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0648); 🇷🇺 Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation

Blokhin National Medical Oncology ( Site 0645); 🇷🇺 Moscow, Moskva, Russian Federation

National Medical Research Radiological Centre ( Site 0660); 🇷🇺 Moscow, Moskva, Russian Federation

City Clinical Hospital 1 na. NI. Pirogov ( Site 0662); 🇷🇺 Moscow, Moskva, Russian Federation

Hadassah Medical-Clinical Research Department ( Site 0920); 🇷🇺 Moscow, Moskva, Russian Federation

First Moscow State Medical University n.a. I.M.Sechenov ( Site 0661); 🇷🇺 Moscow, Moskva, Russian Federation

Privolzhsky District Medical Center ( Site 0655); 🇷🇺 Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation

Samara Regional Clinical Oncology Center ( Site 0656); 🇷🇺 Samara, Samarskaya Oblast, Russian Federation

Road Hospital JSC Russian railways ( Site 0649); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Russian Scientific Center of Radiology and Surgical Technologies ( Site 0665); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

City Clinical Oncology Center ( Site 0646); 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Hospital Universitario de Donostia ( Site 0671); 🇪🇸 San Sebastian, Gipuzkoa, Spain

Hospital Central de Asturias ( Site 0667); 🇪🇸 Oviedo, Asturias, Spain

Tomsk Scientific Research Institute of Oncology ( Site 0657); 🇷🇺 Tomsk, Tomskaya Oblast, Russian Federation

Hospital Universitario Puerta de Hierro ( Site 0678); 🇪🇸 Majadahonda, Madrid, Spain

Complejo Hospitalario Universitario de Santiago ( Site 0668); 🇪🇸 Santiago de Compostela, La Coruna, Spain

Hospital Universitari Vall d Hebron ( Site 0674); 🇪🇸 Barcelona, Spain

Hospital Ramon y Cajal ( Site 0673); 🇪🇸 Madrid, Spain

Hospital General Universitario Gregorio Maranon ( Site 0676); 🇪🇸 Madrid, Spain

Hospital Universitario La Paz ( Site 0677); 🇪🇸 Madrid, Spain

Hospital Universitario Virgen del Rocio ( Site 0670); 🇪🇸 Sevilla, Spain

Hospital Universitario Miguel Servet-Gastroenterology ( Site 0682); 🇪🇸 Zaragoza, Spain

Skane University Hospital ( Site 0692); 🇸🇪 Malmo, Skane Lan, Sweden

Karolinska Universitetssjukhuset, Huddinge ( Site 0689); 🇸🇪 Stockholm, Stockholms Lan, Sweden

Norrlands Universitetssjukhus ( Site 0687); 🇸🇪 Umea, Vasterbottens Lan, Sweden

Universitaetsspital Bern ( Site 0710); 🇨🇭 Bern, Aargau, Switzerland

CHUV (centre hospitalier universitaire vaudois) ( Site 0712); 🇨🇭 Lausanne, Vaud, Switzerland

Kantonsspital St. Gallen ( Site 0708); 🇨🇭 St. Gallen, Sankt Gallen, Switzerland

Sahlgrenska Universitetssjukhuset ( Site 0691); 🇸🇪 Goteborg, Vastra Gotalands Lan, Sweden

National Cheng Kung University Hospital ( Site 0334); 🇨🇳 Tainan, Taiwan

Hopitaux Universitaires de Geneve HUG ( Site 0711); 🇨🇭 Geneve, Switzerland

National Taiwan University Hospital ( Site 0330); 🇨🇳 Taipei, Taiwan

Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0335); 🇨🇳 Kaohsiung, Taiwan

Taipei Veterans General Hospital ( Site 0331); 🇨🇳 Taipei, Taiwan

Chang Gung Medical Foundation. Linkou ( Site 0332); 🇨🇳 Taoyuan, Taiwan

Ramathibodi Hospital. ( Site 0352); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

Siriraj Hospital ( Site 0351); 🇹🇭 Bangkok, Krung Thep Maha Nakhon, Thailand

Maharaj Nakorn Chiangmai Hospital ( Site 0353); 🇹🇭 Chiang Mai, Thailand

Srinagarind Hospital ( Site 0354); 🇹🇭 Khon Kaen, Thailand

Baskent Unv. Adana Uyg. ve Arast. Hastanesi ( Site 0733); 🇹🇷 Adana, Turkey

Adnan Menderes University Medical Faculty ( Site 0737); 🇹🇷 Aydin, Turkey

Bezmialem Vakif University School of Medicine ( Site 0732); 🇹🇷 Istanbul, Turkey

Konya Necmettin Erbakan University Medical Faculty ( Site 0736); 🇹🇷 Konya, Turkey

Inonu University Faculty of Medicine ( Site 0729); 🇹🇷 Malatya, Turkey

VM Medical Park Hastanesi ( Site 0739); 🇹🇷 Mersin, Turkey

Regional Clinical Onco Dispensary_ State Medical University ( Site 0782); 🇺🇦 Chernivtsi, Chernivetska Oblast, Ukraine

National Cancer Institute of the MoH of Ukraine ( Site 0779); 🇺🇦 Kyiv, Kyivska Oblast, Ukraine

ProMedica Flower Hospital ( Site 0090); 🇺🇸 Sylvania, Ohio, United States

Hospital Universitari Parc Tauli ( Site 0681); 🇪🇸 Sabadell, Barcelona, Spain

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie ( Site 0620); 🇵🇱 Lublin, Lubelskie, Poland

SPZOZ MSWIA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie ( Site 0606); 🇵🇱 Olsztyn, Warminsko-mazurskie, Poland

University of Louisville ( Site 0059); 🇺🇸 Louisville, Kentucky, United States

Smilow Cancer Hospital at Yale New Haven ( Site 0042); 🇺🇸 New Haven, Connecticut, United States

James Graham Brown Cancer Center ( Site 0088); 🇺🇸 Louisville, Kentucky, United States

Prince of Wales Hospital ( Site 0268); 🇭🇰 Hong Kong, Hong Kong

Pamela Youde Nethersole Eastern Hospital ( Site 0271); 🇭🇰 Hong Kong, Hong Kong

Tuen Mun Hospital ( Site 0272); 🇭🇰 Tuen Mun, Hong Kong

Queen Mary Hospital ( Site 0267); 🇭🇰 Hong Kong, Hong Kong