Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04210115

Collaborator

(none)

600

Enrollment

159

Locations

Arms

71.8

Anticipated Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Overall Survival (OS) and Event-free Survival (EFS) in:

participants with esophageal squamous cell carcinoma (ESCC),
participants whose tumors express Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10, and
all participants.

The primary study hypotheses are that dCRT+ pembrolizumab is better than dCRT + placebo with respect to:

OS in participants with ESCC,
OS in participants whose tumors express PD-L1 CPS ≥10,
OS in all participants,
EFS in participants with ESCC,
EFS in participants whose tumors express PD-L1 CPS ≥10, and
EFS in all participants.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma (ESCC) Gastroesophageal Junction Carcinoma (GEJC) Esophageal Adenocarcinoma (EAC)	Biological: pembrolizumab Drug: placebo Drug: cisplatin Drug: 5-FU Radiation: radiotherapy Drug: leucovorin Drug: levoleucovorin Drug: oxaliplatin	Phase 3

Detailed Description

Participants receive pembrolizumab or placebo PLUS one of two chemotherapy regimens PLUS radiation therapy for up to approximately one year. The chemotherapy regimens are either:

FP (5-fluorouracil [5-FU] + cisplatin) or
FOLFOX (5-FU + oxaliplatin + leucovorin or levoleucovorin).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled Phase 3 Trial of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Receiving Concurrent Definitive Chemoradiotherapy (KEYNOTE 975)

Actual Study Start Date :

Feb 28, 2020

Anticipated Primary Completion Date :

Feb 21, 2026

Anticipated Study Completion Date :

Feb 21, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: FP therapy: cisplatin 75 mg/m^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)] 1000 mg/m^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray [Gy] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR FOLFOX therapy: oxaliplatin 85 mg/m^2 AND either leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year.	Biological: pembrolizumab IV infusion Other Names: MK-3475 KEYTRUDA® Drug: cisplatin IV infusion Other Names: PLATINOL® Drug: 5-FU IV infusion Other Names: ADRUCIL® Radiation: radiotherapy external radiation Drug: leucovorin IV infusion Other Names: calcium folinate folinic acid Drug: levoleucovorin IV infusion Other Names: FUSILEV® calcium levofolinate levofolinic acid Drug: oxaliplatin IV infusion Other Names: ELOXATIN®
Placebo Comparator: Placebo+FP or FOLFOX Therapy+Radiotherapy Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: FP therapy: cisplatin 75 mg/m^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR FOLFOX therapy: oxaliplatin 85 mg/m^2 AND either leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year.	Drug: placebo IV infusion Other Names: Normal saline solution Drug: cisplatin IV infusion Other Names: PLATINOL® Drug: 5-FU IV infusion Other Names: ADRUCIL® Radiation: radiotherapy external radiation Drug: leucovorin IV infusion Other Names: calcium folinate folinic acid Drug: levoleucovorin IV infusion Other Names: FUSILEV® calcium levofolinate levofolinic acid Drug: oxaliplatin IV infusion Other Names: ELOXATIN®

Arm

Intervention/Treatment

Experimental: Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy

Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either: FP therapy: cisplatin 75 mg/m^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)] 1000 mg/m^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray [Gy] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR FOLFOX therapy: oxaliplatin 85 mg/m^2 AND either leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year.

Biological: pembrolizumab

IV infusion

Other Names:

MK-3475

KEYTRUDA®

Drug: cisplatin

IV infusion

Other Names:

PLATINOL®

Drug: 5-FU

IV infusion

Other Names:

ADRUCIL®

Radiation: radiotherapy

external radiation

Drug: leucovorin

IV infusion

Other Names:

calcium folinate

folinic acid

Drug: levoleucovorin

IV infusion

Other Names:

FUSILEV®

calcium levofolinate

levofolinic acid

Drug: oxaliplatin

IV infusion

Other Names:

ELOXATIN®

Placebo Comparator: Placebo+FP or FOLFOX Therapy+Radiotherapy

Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either: FP therapy: cisplatin 75 mg/m^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR FOLFOX therapy: oxaliplatin 85 mg/m^2 AND either leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle. All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year.

Drug: placebo

IV infusion

Other Names:

Normal saline solution

Drug: cisplatin

IV infusion

Other Names:

PLATINOL®

Drug: 5-FU

IV infusion

Other Names:

ADRUCIL®

Radiation: radiotherapy

external radiation

Drug: leucovorin

IV infusion

Other Names:

calcium folinate

folinic acid

Drug: levoleucovorin

IV infusion

Other Names:

FUSILEV®

calcium levofolinate

levofolinic acid

Drug: oxaliplatin

IV infusion

Other Names:

ELOXATIN®

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) [Up to ~72 months]
OS is defined as the time from randomization to death from any cause.
Event-free Survival (EFS) [Up to ~60 months]
EFS is defined as the time from randomization to an event defined as local, regional, or distant recurrence as assessed by blinded independent central review (BICR) based on imaging or biopsy if indicated (if biopsy is accompanied with radiological recurrence of primary disease as evaluated by investigator); or death from any cause.

Secondary Outcome Measures

Number of participants with an adverse event (AE) [Up to ~15 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.
Number of participants discontinuing study treatment due to an adverse event (AE) [Up to ~12 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Has histologically or cytologically confirmed diagnosis of CTX N+ M0 or cT2-T4a NX M0 ESCC, GEJC, EAC, or histologically or cytologically confirmed diagnosis of cTX N+ M1 cervical or upper thoracic esophageal carcinoma with supraclavicular lymph node metastases only
Is deemed suitable for dCRT
Is ineligible for curative surgery based on the documented opinion of a qualified medical/surgical/radiation oncologist
Is not expected to require tumor resection during the course of the study
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of the first dose of study treatment.
Has adequate organ function
Male participants must use adequate contraception (a male condom plus partner use of an additional contraceptive method) unless confirmed to be azoospermic (vasectomized or secondary to medical cause) and refrain from donating sperm during the study treatment period and through 90 days after the last dose of chemotherapy.
Female participants who are a Woman of Childbearing Potential (WOCBP) must use contraception that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the study treatment period through 180 days after the last dose of chemotherapy or 120 days after the last dose of pembrolizumab, whichever is greater, and agree not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period
Female participants must not be pregnant or breastfeeding

Exclusion Criteria:

Has direct invasion of tumor into adjacent organs such as the aorta or trachea or has radiographic evidence of >90 degree encasement or invasion of a major blood vessel, or of intratumoral cavitation.
Has had major surgery other than for insertion of a feeding tube, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipates the need for major surgery during study treatment; participants with gastric or esophageal fistulae are excluded
Has had weight loss of >20% in the previous 3 months
Has had prior chemotherapy or radiotherapy for esophageal cancer
Has had a myocardial infarction within the past 6 months
Has symptomatic congestive heart failure
Has received prior therapy with an anti-programmed cell death-1 (anti PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed
Has received any prior systemic anticancer therapy for esophageal cancer including investigational agents
Has not recovered from all adverse events (AEs) due to previous non-anticancer therapies to ≤Grade 1 or Baseline
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded from the study. Participants with localized prostate cancer that has undergone potentially curative treatment can be enrolled in the study.
Has severe hypersensitivity (≥Grade 3) to pembrolizumab, any of the study chemotherapy agents, or their excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of Hepatitis B or known active Hepatitis C virus infection
Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment (180 days for participants receiving cisplatin who are breastfeeding)
Has had an allogenic tissue/solid organ transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MemorialCare Health System - Long Beach Medical Center-Oncology ( Site 0691)	Long Beach	California	United States	90806
2	Columbus Regional Research Institute ( Site 0047)	Columbus	Georgia	United States	31904
3	University of Kansas Cancer Center ( Site 0023)	Westwood	Kansas	United States	66205
4	Cancer Center of Kansas ( Site 0058)	Wichita	Kansas	United States	67214
5	University Medical Center ( Site 0035)	New Orleans	Louisiana	United States	70112
6	Greater Baltimore Medical Center ( Site 0031)	Baltimore	Maryland	United States	21204
7	Dana Farber Cancer Center ( Site 0034)	Boston	Massachusetts	United States	02215
8	Henry Ford Hospital ( Site 0685)	Detroit	Michigan	United States	48202
9	University of Missouri ( Site 0688)	Columbia	Missouri	United States	65212
10	Rutgers Cancer Institute of New Jersey ( Site 0695)	New Brunswick	New Jersey	United States	08903
11	Weill Cornell Medical College ( Site 0053)	New York	New York	United States	10065
12	Stephenson Cancer Center ( Site 0044)	Oklahoma City	Oklahoma	United States	73104
13	Oregon Health & Science University Center for Health & Healing 2- CHH2 ( Site 0060)	Portland	Oregon	United States	97239
14	Allegheny Health Network ( Site 0042)	Pittsburgh	Pennsylvania	United States	15212
15	Thompson Cancer Survival Center ( Site 0696)	Knoxville	Tennessee	United States	37916
16	Cancer Care Northwest - Spokane Valley ( Site 0036)	Spokane Valley	Washington	United States	99216
17	University of Wisconsin Hospital and Clinics ( Site 0033)	Madison	Wisconsin	United States	53792
18	Instituto Medico Alexander Fleming ( Site 0063)	Buenos Aires	Caba	Argentina
19	Fundacion Favaloro ( Site 0061)	Ciudad de Buenos Aires	Caba	Argentina	C1093AAS
20	Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0066)	Buenos Aires		Argentina	C1264AAA
21	CEMIC ( Site 0064)	Buenos Aires		Argentina	C1431FWO
22	UCL Saint Luc ( Site 0162)	Brussels	Bruxelles-Capitale, Region De	Belgium	1200
23	UZ Gent ( Site 0163)	Gent	Oost-Vlaanderen	Belgium	9000
24	UZ Leuven ( Site 0161)	Leuven	Vlaams-Brabant	Belgium	3000
25	AZ Delta ( Site 0165)	Roeselare	West-Vlaanderen	Belgium	8800
26	ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0088)	Ijui	Rio Grande Do Sul	Brazil	98700-000
27	Hospital Nossa Senhora da Conceicao ( Site 0087)	Porto Alegre	Rio Grande Do Sul	Brazil	91350-200
28	Clinica de Oncologia Reichow ( Site 0085)	Blumenau	Santa Catarina	Brazil	89010-340
29	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0081)	Sao Paulo		Brazil	01246-000
30	Cross Cancer Institute ( Site 0010)	Edmonton	Alberta	Canada	T6G 1Z2
31	CancerCare Manitoba ( Site 0002)	Winnipeg	Manitoba	Canada	R3E 0V9
32	The Ottawa Hospital - Cancer Care ( Site 0008)	Ottawa	Ontario	Canada	K1H 8L6
33	Sunnybrook Research Institute ( Site 0012)	Toronto	Ontario	Canada	M4N 3M5
34	Princess Margaret Cancer Centre ( Site 0011)	Toronto	Ontario	Canada	M5G 2C4
35	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0005)	Montreal	Quebec	Canada	H2X 0C1
36	Centro Investigación del Cáncer James Lind ( Site 0106)	Temuco	Araucania	Chile	4780000
37	Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0103)	Temuco	Araucania	Chile	4810218
38	Hospital Regional de Concepcion ( Site 0105)	Concepcion	Biobio	Chile	4070038
39	Centro de Cancer Nuestra Senora de la Esperanza ( Site 0104)	Santiago	Region M. De Santiago	Chile	8330024
40	Anhui Provincial Hospital-Oncology Radiotherapy Department ( Site 0531)	Hefei	Anhui	China	230071
41	900 Hospital of the Joint ( Site 0509)	Fuzhou	Fujian	China	350025
42	The First Affiliated Hospital of Xiamen University ( Site 0538)	Xiamen	Fujian	China	361003
43	Hubei Cancer Hospital ( Site 0514)	Wuhan	Hubei	China	430079
44	Hunan Cancer Hospital ( Site 0515)	Changsha	Hunan	China	410006
45	Huai an First People s Hospital ( Site 0526)	Huai An	Jiangsu	China	223001
46	Jiangsu Cancer Hospital ( Site 0519)	Nanjing	Jiangsu	China	210000
47	The Affiliated Hospital of Xuzhou Medical University ( Site 0522)	Xuzhou	Jiangsu	China	221002
48	Affiliated Hospital of Jiangsu University ( Site 0524)	Zhenjiang	Jiangsu	China	212000
49	Jiangxi Cancer Hospital ( Site 0512)	Nanchang	Jiangxi	China	330029
50	Shanghai Chest Hospital ( Site 0503)	Shangai	Shanghai	China	200030
51	Shanghai Chest Hospital ( Site 0501)	Shanghai	Shanghai	China	200030
52	Zhongshan Hospital Fudan University ( Site 0502)	Shanghai	Shanghai	China	200032
53	Sichuan Cancer Hospital ( Site 0527)	Chengdu	Sichuan	China	610041
54	Tianjin Medical University Cancer Institute & Hospital ( Site 0505)	Tianjin	Tianjin	China	300060
55	Hangzhou First People's Hospital ( Site 0530)	Hangzhou	Zhejiang	China	310002
56	Sir Run Run Shaw Hospital ( Site 0523)	Hangzhou	Zhejiang	China	310018
57	Zhejiang Cancer Hospital ( Site 0529)	Hangzhou	Zhejiang	China	310022
58	Rigshospitalet ( Site 0199)	Copenhagen	Hovedstaden	Denmark	2100
59	Odense Universitetshospital ( Site 0200)	Odense	Syddanmark	Denmark	5000
60	SA Pohja-Eesti Regionaalhaigla ( Site 0201)	Tallinn	Harjumaa	Estonia	13419
61	SA Tartu Ulikooli Kliinikum ( Site 0202)	Tartu	Tartumaa	Estonia	51014
62	Institut De Cancerologie De Lorraine ( Site 0222)	Vandoeuvre les Nancy	Ain	France	54519
63	Centre Francois Baclesse ( Site 0236)	Caen	Calvados	France	14075
64	Centre Georges Francois Leclerc ( Site 0223)	Dijon	Cote-d Or	France	21079
65	CHU Limoges Hopital Dupuytren ( Site 0225)	Limoges	Haute-Vienne	France	87042
66	Institut Curie - Centre Rene Huguenin ( Site 0237)	Saint-Cloud	Hauts-de-Seine	France	92210
67	CHU Hotel Dieu Nantes ( Site 0230)	Nantes	Pays-de-la-Loire	France	44093
68	Institut Sainte Catherine ( Site 0228)	Avignon	Provence-Alpes-Cote-d Azur	France	84918
69	CHU Amiens Picardie Site Sud Amiens ( Site 0235)	Amiens	Somme	France	80054
70	CHD Vendee ( Site 0227)	La Roche sur Yon	Vendee	France	85925
71	Marienhospital Stuttgart Vincenz von Paul Kliniken gGmbH ( Site 0253)	Stuttgart	Baden-Wurttemberg	Germany	70199
72	Universitaetsklinikum Koeln ( Site 0251)	Koeln	Nordrhein-Westfalen	Germany	50937
73	Universitaetsklinikum Muenster ( Site 0248)	Muenster	Nordrhein-Westfalen	Germany	48149
74	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz ( Site 0247)	Mainz	Rheinland-Pfalz	Germany	55131
75	Charite Campus Virchow Klinikum ( Site 0250)	Berlin		Germany	13353
76	Facharztzentrum Eppendorf ( Site 0242)	Hamburg		Germany	20249
77	Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0122)	Guatemala		Guatemala	01010
78	Gastrosoluciones ( Site 0126)	Guatemala		Guatemala	01010
79	Oncomedica ( Site 0125)	Guatemala		Guatemala	01010
80	Grupo Medico Angeles ( Site 0121)	Guatemala		Guatemala	01015
81	Medi-K Cayala ( Site 0124)	Guatemala		Guatemala	01016
82	Centro Medico Integral De Cancerología (CEMIC) ( Site 0123)	Quetzaltenango		Guatemala	09002
83	Pamela Youde Nethersole Eastern Hospital ( Site 0543)	Hong Kong		Hong Kong
84	Princess Margaret Hospital. ( Site 0542)	Hong Kong		Hong Kong
85	Queen Mary Hospital ( Site 0541)	Pokfulam		Hong Kong
86	Pecsi Tudomanyegyetem AOK ( Site 0265)	Pecs	Baranya	Hungary	7624
87	Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0262)	Gyula	Bekes	Hungary	5700
88	Orszagos Onkologiai Intezet ( Site 0263)	Budapest		Hungary	1122
89	Debreceni Egyetem Klinikai Kozpont ( Site 0261)	Debrecen		Hungary	4032
90	Fondazione IRCCS Policlinico San Matteo-Oncology ( Site 0300)	Pavia	Lombardia	Italy	27100
91	IRCCS Policlinico San Donato ( Site 0295)	San Donato Milanese	Milano	Italy	20097
92	Azienda Ospedaliero Universitaria Pisana - Presidio Santa Chiara ( Site 0294)	Pisa	Toscana	Italy	56126
93	ASST Papa Giovanni XXIII ( Site 0296)	Bergamo		Italy	24127
94	Azienda Socio Sanitaria Territoriale di Cremona ( Site 0299)	Cremona		Italy	26100
95	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0292)	Milano		Italy	20133
96	Istituto Nazionale Tumori IRCCS Fondazione Pascale-SC Oncologia Clinica Sperimentale Addome ( Site 0	Napoli		Italy	80131
97	IRCCS Istituto Oncologico Veneto ( Site 0298)	Padova		Italy	35128
98	Policlinico Universitario A. Gemelli ( Site 0297)	Roma		Italy	00168
99	Aichi Cancer Center Hospital ( Site 0563)	Nagoya	Aichi	Japan	464-8681
100	National Cancer Center Hospital East ( Site 0562)	Kashiwa	Chiba	Japan	2778577
101	Kanagawa Cancer Center ( Site 0565)	Yokohama	Kanagawa	Japan	241-8515
102	Saitama Cancer Center ( Site 0564)	Kitaadachi-gun	Saitama	Japan	362-0806
103	Shizuoka Cancer Center Hospital and Research Institute ( Site 0566)	Sunto-gun	Shizuoka	Japan	411-8777
104	National Cancer Center Hospital ( Site 0561)	Tokyo		Japan	104-0045
105	Chonnam National University Hwasun Hospital ( Site 0625)	Hwasun Gun	Jeonranamdo	Korea, Republic of	58128
106	National Cancer Center ( Site 0626)	Goyang-si	Kyonggi-do	Korea, Republic of	10408
107	Asan Medical Center ( Site 0623)	Songpagu	Seoul	Korea, Republic of	05505
108	Severance Hospital Yonsei University Health System ( Site 0624)	Seoul		Korea, Republic of	03722
109	Samsung Medical Center ( Site 0622)	Seoul		Korea, Republic of	06351
110	Korea University Guro Hospital ( Site 0621)	Seoul		Korea, Republic of	08308
111	Instituto Nacional de Enfermedades Neoplasicas ( Site 0141)	Lima	Muni Metro De Lima	Peru	Lima 34
112	Hospital Nacional Arzobispo Loayza ( Site 0143)	Lima		Peru	15082
113	Clinica San Gabriel ( Site 0142)	Lima		Peru	15087
114	Baguio General Hospital and Medical Center ( Site 0603)	Baguio City	Benguet	Philippines	2600
115	Cebu Doctors University Hospital ( Site 0604)	Cebu City	Cebu	Philippines	6000
116	The Medical City-Iloilo ( Site 0602)	Iloilo City	Iloilo	Philippines	5000
117	St. Luke s Medical Center ( Site 0601)	Quezon	National Capital Region	Philippines	1102
118	Hospital Beatriz Angelo ( Site 0374)	Loures	Lisboa	Portugal	2674-514
119	Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0372)	Lisboa		Portugal	1099-023
120	CHLN Hospital Santa Maria ( Site 0376)	Lisboa		Portugal	1649-035
121	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0371)	Porto		Portugal	4200-072
122	MedEuropa Bucuresti - Centru de Radioterapie-Oncology ( Site 0400)	București	Bucuresti	Romania	022343
123	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0392)	Cluj-Napoca	Cluj	Romania	400015
124	S.C. Radiotherapy Center Cluj S.R.L ( Site 0391)	Cluj-Napoca	Cluj	Romania	407280
125	S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0394)	Craiova	Dolj	Romania	200347
126	Centrul Medical Topmed ( Site 0398)	Targu-Mures	Mures	Romania	540156
127	S.C.Focus Lab Plus S.R.L ( Site 0395)	Bucuresti		Romania	022548
128	Spitalul Clinic Judetean De Urgenta Constanta ( Site 0393)	Constanta		Romania	900591
129	GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 0430)	Ufa	Baskortostan, Respublika	Russian Federation	450054
130	Kaluga Regional Clinical Oncology Center ( Site 0424)	Kaluga	Kaluzskaja Oblast	Russian Federation	248007
131	Main Military Clinical Hospital n.a. N.N.Burdenko ( Site 0421)	Moscow	Moskva	Russian Federation	105229
132	FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 0429)	Moscow	Moskva	Russian Federation	125367
133	SBHI Samara Regional Clinical Oncology Dispensary ( Site 0420)	Samara	Samarskaya Oblast	Russian Federation	443031
134	Pavlov First Saint Petersburg State Medical University ( Site 0426)	St. Petersburg	Sankt-Peterburg	Russian Federation	197022
135	Medical institute named after Berezin Sergey ( Site 0417)	St. Petersburg	Sankt-Peterburg	Russian Federation	197758
136	Sverdlovsk Regional Oncology Hospital ( Site 0411)	Ekaterinburg	Sverdlovskaya Oblast	Russian Federation	620036
137	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0412)	Kazan	Tatarstan, Respublika	Russian Federation	420029
138	Chang Gung Med Foundation. Kaohsiung Branch ( Site 0643)	Kaohsiung		Taiwan	833
139	China Medical University Hospital ( Site 0646)	Taichung		Taiwan	40447
140	Taichung Veterans General Hospital-Radiation Oncology ( Site 0647)	Taichung		Taiwan	407
141	National Cheng Kung University Hospital ( Site 0645)	Tainan		Taiwan	704
142	National Taiwan University Hospital ( Site 0641)	Taipei		Taiwan	10048
143	Koo Foundation Sun Yat-Sen Cancer Center ( Site 0644)	Taipei		Taiwan	11259
144	Chang Gung Medical Foundation. Linkou ( Site 0642)	Taoyuan		Taiwan	33305
145	İstanbul University Cerrahpaşa Medical Faculty ( Site 0452)	Istambul	Istanbul	Turkey	34098
146	Memorial Ankara Hastanesi ( Site 0461)	Ankara		Turkey	06520
147	Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0451)	Istanbul		Turkey	34722
148	Ege Universitesi Tip Fakultesi ( Site 0457)	Izmir		Turkey	35040
149	Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 0458)	Izmir		Turkey	35360
150	Aberdeen Royal Infirmary ( Site 0474)	Aberdeen	Aberdeen City	United Kingdom	AB25 2ZN
151	Royal Free Hospital ( Site 0702)	London	England	United Kingdom	NW32QG
152	ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 0283)	London	London, City Of	United Kingdom	SW3 6JJ
153	Hammersmith Hospital-Medical Oncology ( Site 0471)	London	London, City Of	United Kingdom	W12 0HS
154	Nottingham University Hospitals NHS Trust ( Site 0476)	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
155	Royal Marsden Hospital (Sutton) ( Site 0281)	Sutton	Surrey	United Kingdom	SM2 5PT
156	University College Hospital NHS Foundation Trust ( Site 0701)	London	Worcestershire	United Kingdom	NW1 2PG
157	Cambridge University Hospitals NHS Trust ( Site 0477)	Cambridge		United Kingdom	CB2 0QQ
158	The Christie NHS Foundation Trust ( Site 0282)	Manchester		United Kingdom	M20 4BX
159	Mount Vernon Hospital ( Site 0478)	Northwood		United Kingdom	HA6 2RN