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)

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase 3 Double-blinded, Two-arm Study to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) Versus Placebo as Adjuvant Therapy in Participants With Hepatocellular Carcinoma and Complete Radiological Response After Surgical Resection or Local Ablation (KEYNOTE-937)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03867084
• Other study ID #: 3475-937
• Secondary ID: MK-3475-937KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 28, 2019
• Est. completion date: August 31, 2029

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 950
• Est. completion date: August 31, 2029
• Est. primary completion date: October 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• Pembrolizumab
IV infusion of Pembrolizumab 200 mg.

Drug:
• Placebo
IV infusion of 0.9% normal saline.

Locations

Country	Name	City	State
Argentina	Fundación favaloro para la Docencia e Investigación Médica ( Site 0808)	Buenos Aires	Caba
Argentina	Hospital Aleman ( Site 0806)	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires ( Site 0792)	Buenos Aires
Argentina	Hospital Italiano ( Site 0793)	Buenos Aires
Argentina	Hospital Universitario Austral ( Site 0795)	Pilar	Buenos Aires
Argentina	Hospital Provincial del Centenario ( Site 0794)	Rosario	Santa Fe
Argentina	Clinica de nefrologia urologia y enfermedades cardiovasculares ( Site 0802)	Santa Fe
Australia	Royal Adelaide Hospital ( Site 0234)	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital AW ( Site 0225)	Camperdown	New South Wales
Australia	Monash Health ( Site 0233)	Clayton	Victoria
Australia	St Vincents Hospital Melbourne ( Site 0227)	Fitzroy	Victoria
Australia	Liverpool Hospital ( Site 0226)	Liverpool	New South Wales
Australia	Alfred Health ( Site 0230)	Melbourne	Victoria
Australia	Royal Perth Hospital ( Site 0229)	Perth	Western Australia
Australia	Princess Alexandra Hospital ( Site 0228)	Woollongabba	Queensland
Belgium	Erasme Hospital ( Site 0376)	Bruxelles	Bruxelles-Capitale, Region De
Belgium	University Hospital Antwerp (UZA) ( Site 0374)	Edegem	Antwerpen
Belgium	UZ Gent ( Site 0375)	Gent	Oost-Vlaanderen
Belgium	UZ Leuven ( Site 0377)	Leuven	Vlaams-Brabant
Brazil	Clinica de Oncologia Reichow ( Site 0818)	Blumenau	Santa Catarina
Brazil	CIONC - Centro Integrado de Oncologia de Curitiba ( Site 0813)	Curitiba	Parana
Brazil	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0820)	Itajai	Santa Catarina
Brazil	Hospital de Clinicas de Porto Alegre ( Site 0824)	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Cancer de Pernambuco ( Site 0815)	Recife	Pernambuco
Brazil	Instituto COI de Pesquisa Educacao e Gestao ( Site 0825)	Rio de Janeiro
Brazil	A.C. Camargo Cancer Center ( Site 0827)	Sao Paulo
Brazil	Casa de Saude Santa Marcelina ( Site 0821)	Sao Paulo
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0826)	Sao Paulo
Brazil	Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 0828)	Sao Paulo
Brazil	Hospital Paulistano ( Site 0829)	São Paulo	Sao Paulo
Bulgaria	Complex Cancer Center Plovdiv-First Medical Oncology Department ( Site 0982)	Plovdiv
Canada	Nova Scotia Health Authority QEII-HSC ( Site 0208)	Halifax	Nova Scotia
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0211)	Montreal	Quebec
Canada	McGill University Health Centre ( Site 0207)	Montreal	Quebec
China	Beijing Cancer Hospital ( Site 0155)	Beijing	Beijing
China	Cancer Hospital Chinese Academy of Medical Sciences ( Site 0156)	Beijing	Beijing
China	Peking University People's Hospital ( Site 0191)	Beijing	Beijing
China	Hunan Cancer Hospital ( Site 0168)	Changsha	Hunan
China	Hunan Provincial People Hospital ( Site 0192)	Changsha	Hunan
China	The Third Xiangya Hospital of Central South University ( Site 0167)	Changsha	Hunan
China	West China Hospital of Sichuan University ( Site 0162)	Chengdu	Sichuan
China	900 Hospital of the Joint ( Site 0197)	Fuzhou	Fujian
China	Fujian Provincial Cancer Hospital ( Site 0165)	Fuzhou	Fujian
China	Guangdong General Hospital ( Site 0166)	Guangzhou	Guangdong
China	Southern Medical University Nanfang Hospital ( Site 0172)	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital ( Site 0171)	Hangzhou	Zhejiang
China	Anhui Provincil Hospital South District ( Site 0181)	Hefei	Anhui
China	Fudan University Shanghai Cancer Center ( Site 0161)	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	Zhongshan Hospital Fudan University ( Site 0193)	Shanghai	Shanghai
China	Affiliated Tumor Hospital of Xinjiang Medical University ( Site 0157)	Urumqi	Xinjiang
China	Hubei Cancer Hospital ( Site 0189)	Wuhan	Hubei
China	Wuhan Union Hospital ( Site 0173)	Wuhan	Hubei
China	The First Affiliated Hospital of Xi an Jiaotong University ( Site 0164)	XI An	Shanxi
Denmark	Aarhus Universitets hospital ( Site 0420)	Aarhus N	Midtjylland
Denmark	Herlev Hospital ( Site 0421)	Herlev	Hovedstaden
Denmark	Odense Universitets Hospital ( Site 0422)	Odense C	Syddanmark
France	Hopital Beaujon ( Site 0439)	Clichy	Hauts-de-Seine
France	Hopital Claude Huriez CHRU LILLE ( Site 0440)	Lille	Nord
France	Hopital de la Timone ( Site 0442)	Marseille	Bouches-du-Rhone
France	CHU Montpellier. ( Site 0443)	Montpellier	Herault
France	CHU Bordeaux Haut-Leveque ( Site 0437)	Pessac	Gironde
France	HUS Hopital Hautepierre ( Site 0445)	Strasbourg	Bas-Rhin
France	CHU Rangueil ( Site 0441)	Toulouse	Haute-Garonne
France	Hopital Paul Brousse ( Site 0447)	Villejuif	Val-de-Marne
Germany	Charite - Campus Virchow Klinikum ( Site 0457)	Berlin
Germany	Staedtisches Klinikum Dresden ( Site 0471)	Dresden	Sachsen
Germany	Universitatsklinikum Carl Gustav Carus ( Site 0459)	Dresden	Sachsen
Germany	Universitaetsklinikum Duesseldorf ( Site 0461)	Duesseldorf	Nordrhein-Westfalen
Germany	Universitaetsklinikum Frankfurt ( Site 0467)	Frankfurt	Hessen
Germany	Krankenhaus Nord-West GmbH ( Site 0472)	Frankfurt am Main	Hessen
Germany	Universitaetsklinikum Hamburg-Eppendorf ( Site 0469)	Hamburg
Germany	Medizinische Hochschule Hannover ( Site 0458)	Hannover	Niedersachsen
Germany	SLK-Kliniken Heilbronn GmbH ( Site 0460)	Heilbronn	Baden-Wurttemberg
Germany	Universitaetsklinikum Koeln ( Site 0463)	Koeln	Nordrhein-Westfalen
Germany	Klinikum rechts der Isar der Technischen Universitaet ( Site 0470)	Muenchen	Bayern
Germany	Universitaetsklinikum Tuebingen ( Site 0466)	Tuebingen	Baden-Wurttemberg
Germany	Universitaetsklinikum Wuerzburg ( Site 0468)	Wuerzburg	Bayern
Hong Kong	Pamela Youde Nethersole Eastern Hospital ( Site 0271)	Hong Kong
Hong Kong	Prince of Wales Hospital ( Site 0268)	Hong Kong
Hong Kong	Queen Mary Hospital ( Site 0267)	Hong Kong
Hong Kong	Tuen Mun Hospital ( Site 0272)	Tuen Mun
Hungary	Semmelweis University ( Site 0480)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont Onkologiai Tanszek ( Site 0481)	Debrecen
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház-Oncology center ( Site 0484)	Kaposvár	Somogy
Hungary	Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 0483)	Kecskemét	Bacs-Kiskun
Hungary	SZTE Szent-Gyorgyi Albert Klinikai Kozpont ( Site 0482)	Szeged	Csongrad
Ireland	St Vincent's University Hospital ( Site 0498)	Dublin
Ireland	Tallaght University Hospital ( Site 0499)	Dublin
Israel	Rambam Medical Center ( Site 0524)	Haifa
Israel	Haddassah Medical Organization - Ein Kerem ( Site 0519)	Jerusalem
Israel	Rabin Medical Center ( Site 0520)	Petah Tikva
Israel	Chaim Sheba Medical Center ( Site 0523)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0522)	Tel Aviv
Italy	Istituto Tumori Giovanni Paolo II ( Site 0543)	Bari
Italy	AOU di Bologna Policliico S. Orsola-Malpighi ( Site 0541)	Bologna
Italy	Azienda Ospedaliero Universitaria Careggi ( Site 0549)	Firenze
Italy	Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 0550)	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0540)	Milano
Italy	A O U Policlinico di Modena ( Site 0548)	Modena	Abruzzo
Italy	Ospedale del Mare ( Site 0545)	Napoli
Italy	Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello ( Site 0547)	Palermo	Sicilia
Italy	Azienda Ospedaliero Universitaria Pisana ( Site 0546)	Pisa
Italy	Azienda Ospedaliera Ordine Mauriziano di Torino ( Site 0542)	Torino	Piemonte
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	Saitama Medical University Hospital ( Site 0104)	Iruma-gun	Saitama
Japan	Kanazawa University Hospital ( Site 0111)	Kanazawa	Ishikawa
Japan	Toranomon Hospital Kajigaya ( Site 0109)	Kawasaki	Kanagawa
Japan	Kagawa University Hospital ( Site 0121)	Kita-gun	Kagawa
Japan	Kurume University Hospital ( Site 0119)	Kurume	Fukuoka
Japan	University Hospital, Kyoto Prefectural University of Medicine ( Site 0112)	Kyoto
Japan	Kyorin University Hospital ( Site 0106)	Mitaka	Tokyo
Japan	Musashino Red Cross Hospital ( Site 0107)	Musashino	Tokyo
Japan	Japanese Red Cross Osaka Hospital ( Site 0113)	Osaka
Japan	Osaka Metropolitan University Hospital. ( Site 0114)	Osaka
Japan	Kindai University Hospital ( Site 0116)	Osakasayama	Osaka
Japan	Saga-Ken Medical Centre Koseikan ( Site 0120)	Saga
Japan	Hokkaido P.W.F.A.C Sapporo-Kosei General Hospital ( Site 0102)	Sapporo	Hokkaido
Japan	Kagawa Prefectural Central Hospital ( Site 0122)	Takamatsu	Kagawa
Japan	The University of Tokyo Hospital ( Site 0105)	Tokyo
Japan	Toranomon Hospital ( Site 0108)	Tokyo
Japan	Ehime University Hospital ( Site 0123)	Toon	Ehime
Japan	Wakayama Medical University Hospital ( Site 0115)	Wakayama
Japan	Yokohama City University Medical Center ( Site 0110)	Yokohama	Kanagawa
Korea, Republic of	National Cancer Center ( Site 0314)	Goyang-si	Kyonggi-do
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0313)	Seongnam-si	Kyonggi-do
Korea, Republic of	Asan Medical Center ( Site 0310)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 0311)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0312)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 0309)	Seoul
Korea, Republic of	The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 0315)	Seoul
Malaysia	Penang Adventist Hospital ( Site 0289)	George Town	Pulau Pinang
Malaysia	University Malaya Medical Centre ( Site 0288)	Kuala Lumpur
Malaysia	Hospital Universiti Sains Malaysia ( Site 0295)	Kubang Kerian	Kelantan
Malaysia	Sarawak General Hospital ( Site 0293)	Kuching	Sarawak
Malaysia	Gleneagles Penang ( Site 0290)	Penang	Pulau Pinang
Malaysia	Institut Kanser Negara - National Cancer Institute ( Site 0294)	Putrajaya Wilayah Persekutuan	Wilayah Persekutuan Putrajaya
New Zealand	Auckland City Hospital ( Site 0246)	Auckland
New Zealand	Christchurch Hospital ( Site 0247)	Christchurch	Canterbury
Norway	Oslo Universitetssykehus HF. Ulleval ( Site 0433)	Oslo
Poland	Copernicus PL Sp. z o.o. ( Site 0603)	Gdansk	Pomorskie
Poland	Szpital Wojewodzki im. Mikolaja Kopernika ( Site 0604)	Koszalin	Zachodniopomorskie
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie ( Site 0620)	Lublin	Lubelskie
Poland	ID Clinic ( Site 0619)	Myslowice	Slaskie
Poland	SPZOZ MSWIA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie ( Site 0606)	Olsztyn	Warminsko-mazurskie
Poland	Izerskie Centrum Pulmonologii i Chemioterapii IZER-MED Spolka z o.o. ( Site 0607)	Szklarska Poreba	Dolnoslaskie
Poland	MTZ Clinical Research Sp. z o. o. ( Site 0608)	Warsaw	Mazowieckie
Russian Federation	Altay Regional Oncology Dispensary ( Site 0919)	Barnaul	Altayskiy Kray
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0648)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	Siberian Clinical Center of FMBA ( Site 0918)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	Blokhin National Medical Oncology ( Site 0645)	Moscow	Moskva
Russian Federation	City Clinical Hospital 1 na. NI. Pirogov ( Site 0662)	Moscow	Moskva
Russian Federation	First Moscow State Medical University n.a. I.M.Sechenov ( Site 0661)	Moscow	Moskva
Russian Federation	Hadassah Medical-Clinical Research Department ( Site 0920)	Moscow	Moskva
Russian Federation	National Medical Research Radiological Centre ( Site 0660)	Moscow	Moskva
Russian Federation	Privolzhsky District Medical Center ( Site 0655)	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	City Clinical Oncology Center ( Site 0646)	Saint Petersburg	Sankt-Peterburg
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	Samara Regional Clinical Oncology Center ( Site 0656)	Samara	Samarskaya Oblast
Russian Federation	Tomsk Scientific Research Institute of Oncology ( Site 0657)	Tomsk	Tomskaya Oblast
Spain	Hospital Universitari Vall d Hebron ( Site 0674)	Barcelona
Spain	Hospital General Universitario Gregorio Maranon ( Site 0676)	Madrid
Spain	Hospital Ramon y Cajal ( Site 0673)	Madrid
Spain	Hospital Universitario La Paz ( Site 0677)	Madrid
Spain	Hospital Universitario Puerta de Hierro ( Site 0678)	Majadahonda	Madrid
Spain	Hospital Central de Asturias ( Site 0667)	Oviedo	Asturias
Spain	Hospital Universitari Parc Tauli ( Site 0681)	Sabadell	Barcelona
Spain	Hospital Universitario de Donostia ( Site 0671)	San Sebastian	Gipuzkoa
Spain	Complejo Hospitalario Universitario de Santiago ( Site 0668)	Santiago de Compostela	La Coruna
Spain	Hospital Universitario Virgen del Rocio ( Site 0670)	Sevilla
Spain	Hospital Universitario Miguel Servet-Gastroenterology ( Site 0682)	Zaragoza
Sweden	Sahlgrenska Universitetssjukhuset ( Site 0691)	Goteborg	Vastra Gotalands Lan
Sweden	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
Switzerland	University Hospital Basel ( Site 0709)	Basel	Basel-Stadt
Switzerland	Universitaetsspital Bern ( Site 0710)	Bern	Aargau
Switzerland	Hopitaux Universitaires de Geneve HUG ( Site 0711)	Geneve
Switzerland	CHUV (centre hospitalier universitaire vaudois) ( Site 0712)	Lausanne	Vaud
Switzerland	Kantonsspital St. Gallen ( Site 0708)	St. Gallen	Sankt Gallen
Switzerland	Kantonsspital Winterthur ( Site 0714)	Winterthur	Zurich
Switzerland	Universitaetsspital Zurich ( Site 0713)	Zurich
Taiwan	Chang Gung Medical Foundation. Kaohsiung Branch ( Site 0335)	Kaohsiung
Taiwan	China Medical University Hospital ( Site 0333)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 0334)	Tainan
Taiwan	National Taiwan University Hospital ( Site 0330)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 0331)	Taipei
Taiwan	Chang Gung Medical Foundation. Linkou ( Site 0332)	Taoyuan
Thailand	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
Turkey	Baskent Unv. Adana Uyg. ve Arast. Hastanesi ( Site 0733)	Adana
Turkey	Ankara Sehir Hastanesi ( Site 0731)	Ankara
Turkey	Gulhane Egitim ve Arastirma Hastanesi ( Site 0741)	Ankara
Turkey	Adnan Menderes University Medical Faculty ( Site 0737)	Aydin
Turkey	Acibadem Maslak Hastanesi ( Site 0742)	Istanbul
Turkey	Bezmialem Vakif University School of Medicine ( Site 0732)	Istanbul
Turkey	Göztepe Prof. Dr. Süleyman Yalçin Sehir Hastanesi-oncology ( Site 0730)	Istanbul
Turkey	Dokuz Eylul Universitesi ( Site 0740)	Izmir
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	Namik Kemal Universitesi Tip Fakultesi ( Site 0738)	Tekirdag	Tekirdas
Ukraine	Regional Clinical Onco Dispensary_ State Medical University ( Site 0782)	Chernivtsi	Chernivetska Oblast
Ukraine	Regional Oncology Center of Kharkiv ( Site 0777)	Kharkiv	Kharkivska Oblast
Ukraine	Medical Center Dobrobut Clinic ( Site 0785)	Kyiv
Ukraine	National Cancer Institute of the MoH of Ukraine ( Site 0779)	Kyiv	Kyivska Oblast
Ukraine	Shalimov s NI of Surgery and Transplantation ( Site 0781)	Kyiv	Kyivska Oblast
Ukraine	Universal Clinic Oberig-Oncology Center ( Site 0786)	Kyiv
Ukraine	MI Odessa Regional Oncological Centre ( Site 0776)	Odesa	Odeska Oblast
Ukraine	CI City Clinical Hospital # 3 ( Site 0783)	Zaporizhzhia	Zaporizka Oblast
United Kingdom	Belfast City Hospital ( Site 0752)	Belfast	Northern Ireland
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0757)	Birkenhead	Wirral
United Kingdom	Cambridge University Hospitals NHS Trust ( Site 0755)	Cambridge	Cambridgeshire
United Kingdom	University Hospital Coventry and Warwickshire NHS Trust ( Site 0754)	Coventry
United Kingdom	The Beatson West of Scotland Cancer Centre ( Site 0750)	Glasgow	Glasgow City
United Kingdom	Leeds Teaching Hospitals NHS Trust ( Site 0751)	Leeds
United Kingdom	Kings College Hospital NHS Foundation Trust ( Site 0758)	London	London, City Of
United Kingdom	Nottingham University Hospitals NHS Trust ( Site 0756)	Nottingham
United Kingdom	Weston Park Hospital ( Site 0753)	Sheffield	Derbyshire
United States	University of New Mexico ( Site 0041)	Albuquerque	New Mexico
United States	Beth Israel Deaconess Medical Ctr. ( Site 0033)	Boston	Massachusetts
United States	Boston Medical Center ( Site 0025)	Boston	Massachusetts
United States	Massachusetts General Hospital ( Site 0062)	Boston	Massachusetts
United States	Miami Valley Hospital South ( Site 0093)	Centerville	Ohio
United States	University of Cincinnati Medical Center ( Site 0084)	Cincinnati	Ohio
United States	Henry Ford Hospital-GI/Hepatology Research ( Site 0047)	Detroit	Michigan
United States	City of Hope Medical Center ( Site 0027)	Duarte	California
United States	Regional Cancer Center ( Site 0054)	Fort Myers	Florida
United States	Banner MD Anderson Cancer Center ( Site 0026)	Gilbert	Arizona
United States	Indiana University Simon Cancer Center ( Site 0075)	Indianapolis	Indiana
United States	University of Iowa ( Site 0067)	Iowa City	Iowa
United States	North Shore-Long Island Jewish Health System ( Site 0068)	Lake Success	New York
United States	James Graham Brown Cancer Center ( Site 0088)	Louisville	Kentucky
United States	University of Louisville ( Site 0059)	Louisville	Kentucky
United States	Vanderbilt Ingram Cancer Center ( Site 0006)	Nashville	Tennessee
United States	Smilow Cancer Hospital at Yale New Haven ( Site 0042)	New Haven	Connecticut
United States	University Medical Center New Orleans ( Site 0014)	New Orleans	Louisiana
United States	Stephenson Cancer Center ( Site 0045)	Oklahoma City	Oklahoma
United States	Virginia Mason Medical Center ( Site 0028)	Seattle	Washington
United States	ProMedica Flower Hospital ( Site 0090)	Sylvania	Ohio
United States	Baylor Scott & White Medical Center - Temple ( Site 0089)	Temple	Texas
United States	The University of Arizona Cancer Center - North Campus ( Site 0039)	Tucson	Arizona
United States	University of Massachusetts Worcester ( Site 0017)	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Denmark,  France,  Germany,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  New Zealand,  Norway,  Poland,  Russian Federation,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence-Free Survival (RFS)	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.	Up to ~6 years
Primary	Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to ~8 years
Secondary	Percentage of Participants who Experience an Adverse Event (AE)	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.	Up to ~8 years
Secondary	Percentage of Participants who Discontinue Study Treatment Due to an AE	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.	Up to ~1 year
Secondary	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	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.	Baseline and time of last patient reported outcome (PRO) assessment (up to ~5 years)
Secondary	Change from Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Scale Score	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.	Baseline and time of last PRO assessment (up to ~5 years)
Secondary	Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score	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.	Baseline and time of last PRO assessment (up to ~5 years)

External Links

•   Merck Clinical Trials Information
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