Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)
- Conditions
- Head and Neck Neoplasms
- Interventions
- Drug: PlaceboRadiation: Accelerated Fractionation (AFX) RadiotherapyRadiation: Standard Fractionation (SFX) Radiotherapy
- Registration Number
- NCT03040999
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to determine the efficacy and safety of pembrolizumab given concomitantly with chemoradiation (CRT) and as maintenance therapy versus placebo plus CRT in participants with locally advanced head and neck squamous cell carcinoma (LA HNSCC). The primary hypothesis is that pembrolizumab in combination with CRT is superior to placebo in combination with CRT with respect to event-free survival (EFS).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 804
- Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell carcinoma. Participants with oral cavity tumors need to have unresectable disease. Participants with multiple synchronous tumors are not eligible for the study.
- Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy. If an excisional or incisional biopsy has been performed, participants remain eligible for the study provided the residual disease meets the staging criteria required for the trial (e.g., excisional biopsy of a lymph node with residual T4 primary). Prior surgical debulking, including tonsillectomy, for the head and neck cancer under study is not allowed.
- Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1
- Is eligible for definitive CRT and not considered for primary surgery based on investigator decision
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days prior to receiving the first dose of study therapy
- Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
- Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy
- Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
- Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with pembrolizumab
- Has received a live vaccine within 30 days prior to the first dose of study therapy
- Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer
- Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for head and neck cancer under study
- Has not recovered from major surgery prior to starting study therapy
- Has known active Hepatitis B or C
- Has known history of Human Immunodeficiency Virus (HIV)
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
- Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has had previous allogeneic tissue/solid organ transplant
- Has active infection requiring systemic therapy
- Has a history of severe hypersensitivity reaction to pembrolizumab, Cisplatin or radiotherapy or their analogs
- Is pregnant or breast feeding or expecting to conceive or father children throughout the study period and for up to 180 days after the last dose of study therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Cisplatin + CRT Pembrolizumab Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab. Pembrolizumab + Cisplatin + CRT Accelerated Fractionation (AFX) Radiotherapy Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab. Pembrolizumab + Cisplatin + CRT Standard Fractionation (SFX) Radiotherapy Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab. Placebo + Cisplatin + CRT Placebo Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo. Placebo + Cisplatin + CRT Accelerated Fractionation (AFX) Radiotherapy Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo. Placebo + Cisplatin + CRT Standard Fractionation (SFX) Radiotherapy Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo. Pembrolizumab + Cisplatin + CRT Cisplatin Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab. Placebo + Cisplatin + CRT Cisplatin Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo.
- Primary Outcome Measures
Name Time Method Event-free Survival (EFS) Up to approximately 62 months EFS is the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery \>20 weeks from end of CRT when invasive cancer is present. From product-limit (Kaplan-Meier) method for censored data.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Physical Functioning Prior to the first dose of study treatment (Baseline) and up to Week 45 Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better quality of life. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.
Number of Participants With Adverse Events (AEs) From time of first dose of study treatment until 90 days after last dose (up to approximately 19 months) An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.
Number of Participants Discontinuing Study Drug Due to an AE From time of first dose of study treatment until the end of treatment (up to approximately 16 months) An AE is any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy.
Overall Survival (OS) Up to approximately 62 months OS is the time from randomization to death due to any cause, from product-limit (Kaplan-Meier) method for censored data. The hypothesis was that pembrolizumab in combination with CRT is superior to placebo in combination with CRT; but based on the protocol, because the statistical criterion for success in the primary EFS hypothesis was not met, the OS hypothesis was not tested
Change From Baseline in Global Health Status/Quality of Life (GHS/QoL) Prior to the first dose of study treatment (Baseline) and up to Week 45 The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) contains 30 items and measures five functional dimensions (physical, role, emotional, cognitive and social), three symptom items (fatigue, nausea/vomiting, and pain), six single items (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and QoL scale. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100, so that a higher score indicates a better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.
Change From Baseline in Swallowing, Speech, and Pain Symptoms Prior to the first dose of study treatment (Baseline) and up to Week 45 EORTC QLQ Head and Neck Questionnaire (H\&N35) consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality), Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing, speech, and pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H\&N35 is considered as clinically relevant. Based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.
Trial Locations
- Locations (151)
UCLA Medical Center ( Site 0273)
🇺🇸Los Angeles, California, United States
Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1007)
🇵🇱Gdynia, Poland
Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie ( Site 1000)
🇵🇱Warszawa, Poland
Noordwest Ziekenhuisgroep NWZ ( Site 1350)
🇳🇱Alkmaar, Netherlands
Erasmus University Medical Center ( Site 1354)
🇳🇱Rotterdam, Netherlands
Oncology Hematology Care, Inc. ( Site 8003)
🇺🇸Cincinnati, Ohio, United States
Indiana University ( Site 0264)
🇺🇸Indianapolis, Indiana, United States
Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0269)
🇺🇸Seattle, Washington, United States
Hospital Nossa Senhora da Conceicao ( Site 0001)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Ipswich Hospital ( Site 1207)
🇬🇧Ipswich, Suffolk, United Kingdom
University of California San Francisco ( Site 0274)
🇺🇸San Francisco, California, United States
Hospital Pablo Tobon Uribe ( Site 0151)
🇨🇴Medellin, Antioquia, Colombia
Centro de Investigacion Clinica del Country ( Site 0155)
🇨🇴Bogota, Colombia
Linkou Chang Gung Memorial Hospital ( Site 0502)
🇨🇳Taoyuan, Taiwan
Fundacion Valle del Lili ( Site 0150)
🇨🇴Cali, Valle Del Cauca, Colombia
Centro Medico Imbanaco de Cali S.A ( Site 0156)
🇨🇴Cali, Valle Del Cauca, Colombia
Medical Oncology Associates (Summit Cancer Centers) ( Site 0257)
🇺🇸Spokane, Washington, United States
Liverpool Hospital ( Site 0301)
🇦🇺Liverpool, New South Wales (Australia), Australia
Rush University Medical Center ( Site 0260)
🇺🇸Chicago, Illinois, United States
Universitaetsklinikum Schleswig-Holstein-Campus Luebeck ( Site 0803)
🇩🇪Luebeck, Germany
Institut Gustave Roussy ( Site 0759)
🇫🇷Villejuif, France
Hospital Santa Izabel - Santa Casa de Misericordia da Bahia ( Site 0006)
🇧🇷Salvador, Bahia, Brazil
Clinique et Maternite Sainte-Elisabeth ( Site 0653)
🇧🇪Namur, Belgium
Landeskrankenhaus - Universitatsklinikum Graz ( Site 0601)
🇦🇹Graz, Austria
Krankenhaus der Barmherzigen Schwestern Linz ( Site 0603)
🇦🇹Linz, Austria
Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0003)
🇧🇷Barretos, Sao Paulo, Brazil
Liga Norte Riograndense Contra o Cancer ( Site 0005)
🇧🇷Natal, Rio Grande Do Norte, Brazil
Istituto Oncologico Veneto ( Site 0957)
🇮🇹Padova, Italy
Cliniques Universitaires Saint Luc - Bruxelles ( Site 0651)
🇧🇪Brussels, Belgium
Princess Margaret Cancer Centre ( Site 0051)
🇨🇦Toronto, Ontario, Canada
Royal Adelaide Hospital ( Site 0303)
🇦🇺Adelaide, South Australia, Australia
Istituto Europeo di Oncologia ( Site 0953)
🇮🇹Milano, Italy
Azienda Ospedaliera San Paolo ( Site 0952)
🇮🇹Milano, Italy
Kagawa University Hospital ( Site 0359)
🇯🇵Kita-gun, Kagawa, Japan
St. Luke's Cancer Center - Anderson ( Site 0251)
🇺🇸Easton, Pennsylvania, United States
H.U. Vall de Hebron ( Site 1052)
🇪🇸Barcelona, Spain
Hospital Clinico San Carlos ( Site 1051)
🇪🇸Madrid, Spain
Hospital Doce de Octubre ( Site 1054)
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal ( Site 1055)
🇪🇸Madrid, Spain
Ankara Sehir Hastanesi ( Site 1108)
🇹🇷Ankara, Turkey
Norfolk & Norwich University Hospital NHS Foundation Trust ( Site 1206)
🇬🇧Norwich, Norfolk, United Kingdom
Barbara Ann Karmanos Cancer Institute ( Site 0272)
🇺🇸Detroit, Michigan, United States
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0057)
🇨🇦Sherbrooke, Quebec, Canada
McGill University Health Centre ( Site 0061)
🇨🇦Montreal, Quebec, Canada
Cross Cancer Institute ( Site 0064)
🇨🇦Edmonton, Alberta, Canada
University Hospital Southampton NHS Foundation Trust ( Site 1203)
🇬🇧Southampton, United Kingdom
Royal Marsden NHS Foundation Trust ( Site 1201)
🇬🇧Sutton, United Kingdom
Medical Park Izmir Hastanesi ( Site 1109)
🇹🇷Izmir, Turkey
Hospital Duran i Reynals ( Site 1053)
🇪🇸Hospitalet de Llobregat, Spain
Hospital Universitario Virgen de la Victoria ( Site 1056)
🇪🇸Malaga, Spain
SRH Waldklinikum Gera GmbH ( Site 0802)
🇩🇪Gera, Germany
Universitares Cancer Center Hamburg - UCCH ( Site 0811)
🇩🇪Hamburg, Germany
St. Joseph Heritage Healthcare ( Site 0254)
🇺🇸Santa Rosa, California, United States
Mary Bird Perkins Cancer Center at St. Tammany Parish Hospital ( Site 0281)
🇺🇸Baton Rouge, Louisiana, United States
University of Massachusetts Memorial Medical Center ( Site 0285)
🇺🇸Worcester, Massachusetts, United States
Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center ( Site 0290)
🇺🇸Springfield, Missouri, United States
University of Rochester - James P. Wilmot Cancer Center ( Site 0255)
🇺🇸Rochester, New York, United States
University of Virginia Health System ( Site 0261)
🇺🇸Charlottesville, Virginia, United States
Texas Oncology PA ( Site 8001)
🇺🇸Longview, Texas, United States
Comprehensive Cancer Centers of Nevada ( Site 8004)
🇺🇸Las Vegas, Nevada, United States
St. Francis Hospital Cancer Center ( Site 1461)
🇺🇸Greenville, South Carolina, United States
Willamette Valley Cancer Institute and Research Center ( Site 8000)
🇺🇸Eugene, Oregon, United States
Texas Oncology-Arlington North ( Site 8005)
🇺🇸Arlington, Texas, United States
Blacktown Hospital Western Sydney Local Health District ( Site 0304)
🇦🇺Blacktown, New South Wales, Australia
Princess Alexandra Hospital ( Site 0305)
🇦🇺Brisbane, Queensland, Australia
Royal Brisbane and Women s Hospital ( Site 0302)
🇦🇺Herston, Queensland, Australia
Peter MacCallum Cancer Centre ( Site 0300)
🇦🇺Melbourne, Victoria, Australia
Landeskrankenhaus Salzburg ( Site 0600)
🇦🇹Salzburg, Austria
Allgemeines Krankenhaus der Stadt Wien ( Site 0602)
🇦🇹Vienna/Wien, Austria
UZ Leuven Campus Gasthuisberg ( Site 0652)
🇧🇪Leuven, Belgium
UZ Gent ( Site 0650)
🇧🇪Gent, Belgium
C.H.U. Sart Tilman-Service d'Oncologie Medicale ( Site 0654)
🇧🇪Liege, Belgium
Centro Regional Integrado de Oncologia ( Site 0002)
🇧🇷Fortaleza, Ceara, Brazil
Hospital de Clinicas de Porto Alegre ( Site 0011)
🇧🇷Porto Alegre, RS, Brazil
Instituto do Cancer de Sao Paulo - ICESP ( Site 0004)
🇧🇷Sao Paulo, SP, Brazil
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0010)
🇧🇷Rio de Janeiro, Brazil
Hospital das Clinicas da FMUSP de Ribeirao Preto ( Site 0008)
🇧🇷Ribeirao Preto, Brazil
Tom Baker Cancer Centre ( Site 0063)
🇨🇦Calgary, Alberta, Canada
Fakultni nemocnice Olomouc ( Site 0701)
🇨🇿Olomouc, Czechia
London Health Sciences Centre ( Site 0055)
🇨🇦London, Ontario, Canada
Juravinski Cancer Centre ( Site 0062)
🇨🇦Hamilton, Ontario, Canada
The Ottawa Hospital - Cancer Care ( Site 0052)
🇨🇦Ottawa, Ontario, Canada
Fakultni nemocnice Ostrava ( Site 0702)
🇨🇿Ostrava, Czechia
Fakultni Nemocnice Hradec Kralove ( Site 0705)
🇨🇿Hradec Kralove, Czechia
Nemocnice Na Bulovce ( Site 0700)
🇨🇿Praha 8, Czechia
FN Brno. ( Site 0703)
🇨🇿Brno, Czechia
Institut Claudius Regaud ( Site 0754)
🇫🇷Toulouse Cedex 09, France
Clinique Francois Chenieux ( Site 0757)
🇫🇷Limoges, France
2. LF UK a FN Motol ( Site 0704)
🇨🇿Praha, Czechia
Centre Jean Bernard Laboratoire Mahe Meziani ( Site 0760)
🇫🇷Le Mans, France
Institut De Cancerologie De Lorraine ( Site 0758)
🇫🇷Vandoeuvre les Nancy, France
Universitätsklinikum Erlangen ( Site 0801)
🇩🇪Erlangen, Germany
Medizinische Hochschule Hannover ( Site 0807)
🇩🇪Hannover, Germany
Universitaetsklinik Ulm ( Site 0804)
🇩🇪Ulm, Germany
Klinikum der Universitaet Munchen ( Site 0810)
🇩🇪Munchen, Germany
Rambam MC ( Site 0903)
🇮🇱Haifa, Israel
Hadassah Ein Karem Jerusalem ( Site 0902)
🇮🇱Jerusalem, Israel
Rabin Medical Center ( Site 0904)
🇮🇱Petah Tikva, Israel
Azienda Ospedaliero Universitaria Careggi ( Site 0955)
🇮🇹Firenze, Italy
Sheba MC ( Site 0901)
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center ( Site 0900)
🇮🇱Tel Aviv, Israel
Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0954)
🇮🇹Modena, MO, Italy
Istituto Nazionale Tumori ( Site 0950)
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0951)
🇮🇹Napoli, Italy
Fondazione IRCCS - Policlinico San Matteo ( Site 0960)
🇮🇹Pavia, Italy
Hyogo Cancer Center ( Site 0354)
🇯🇵Akashi, Hyogo, Japan
Hokkaido University Hospital ( Site 0351)
🇯🇵Sapporo, Hokkaido, Japan
National Cancer Center Hospital East ( Site 0350)
🇯🇵Kashiwa, Chiba, Japan
Miyagi Cancer Center ( Site 0353)
🇯🇵Natori, Miyagi, Japan
Hiroshima University Hospital ( Site 0352)
🇯🇵Hiroshima, Japan
Chiba Cancer Center ( Site 0358)
🇯🇵Chiba, Japan
Seoul National University Bundang Hospital ( Site 0453)
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Osaka International Cancer Institute ( Site 0355)
🇯🇵Osaka, Japan
The Cancer Institute Hospital of JFCR ( Site 0357)
🇯🇵Tokyo, Japan
Chungbuk National University Hospital ( Site 0454)
🇰🇷Cheongju si, Chungcheongbuk Do, Korea, Republic of
Medical Hospital, Tokyo Medical And Dental University ( Site 0356)
🇯🇵Tokyo, Japan
Chungnam National University Hospital ( Site 0455)
🇰🇷Daejeon, Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 0452)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 0450)
🇰🇷Seoul, Korea, Republic of
UMCG ( Site 1351)
🇳🇱Groningen, Netherlands
UMC St. Radboud ( Site 1356)
🇳🇱Nijmegen, Netherlands
VU Medisch Centrum ( Site 1352)
🇳🇱Amsterdam, Netherlands
Mazowiecki Szpital Onkologiczny ( Site 1015)
🇵🇱Wieliszew, Mazowieckie, Poland
Dolnoslaskie Centrum Onkologii. ( Site 1001)
🇵🇱Wroclaw, Dolnoslaskie, Poland
Capital & Coast District Health Board - Wellington Hospital ( Site 0400)
🇳🇿Wellington, Newtown, New Zealand
Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1005)
🇵🇱Bielsko-Biala, Poland
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 1008)
🇵🇱Krakow, Poland
Hospital Gral Universitario de Valencia ( Site 1050)
🇪🇸Valencia, Spain
Zachodniopomorskie Centrum Onkologii ( Site 1013)
🇵🇱Szczecin, Poland
Chang Gung Medical Foundation - Kaohsiung ( Site 0501)
🇨🇳Kaohsiung, Taiwan
National Cheng Kung University Hospital ( Site 0503)
🇨🇳Tainan, Taiwan
National Taiwan University Hospital ( Site 0500)
🇨🇳Taipei, Taiwan
Taichung Veterans General Hospital ( Site 0506)
🇨🇳Taichung, Taiwan
MacKay Memorial Hospital ( Site 0505)
🇨🇳Taipei, Taiwan
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1102)
🇹🇷Ankara, Turkey
Taipei Veterans General Hospital ( Site 0504)
🇨🇳Taipei, Taiwan
Basken Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 1103)
🇹🇷Adana, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi ( Site 1100)
🇹🇷Istanbul, Turkey
Medipol Universite Hastanesi ( Site 1104)
🇹🇷Istanbul, Turkey
Kocaeli Universitesi Tip Fakultesi ( Site 1106)
🇹🇷Kocaeli, Turkey
Inonu Universitesi Tip Fakultesi ( Site 1101)
🇹🇷Malatya, Turkey
University Hospital of North Staffordshire ( Site 1202)
🇬🇧Stoke-On-Trent, Staffordshire, United Kingdom
Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1204)
🇬🇧London, United Kingdom
The Royal Marsden Foundation Trust ( Site 1200)
🇬🇧London, United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust ( Site 1208)
🇬🇧Preston, United Kingdom
St Bartholomew s Hospital ( Site 1205)
🇬🇧London, United Kingdom
Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie ( Site 1010)
🇵🇱Gliwice, Poland
Smilow Cancer Hospital at Yale New Haven ( Site 0256)
🇺🇸New Haven, Connecticut, United States
University of Michigan Hospital and Health Systems ( Site 0267)
🇺🇸Ann Arbor, Michigan, United States
Texas Oncology-Austin Central ( Site 8002)
🇺🇸Austin, Texas, United States
St. Vincent Healthcare Frontier Cancer Center ( Site 0286)
🇺🇸Billings, Montana, United States