Efficacy and Safety of Pembrolizumab (MK-3475) With Platinum Doublet Chemotherapy as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Non-small Cell Lung Cancer (MK-3475-671/KEYNOTE-671)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03425643

Collaborator

(none)

786

Enrollment

227

Locations

Arms

98.2

Anticipated Duration (Months)

3.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial will evaluate the safety and efficacy of pembrolizumab (MK-3475) in combination with platinum doublet neoadjuvant chemotherapy (NAC) before surgery [neoadjuvant phase], followed by pembrolizumab alone after surgery [adjuvant phase] in participants with resectable stage II, IIIA, and resectable IIIB (T3-4N2) non-small cell lung cancer (NSCLC). The primary hypotheses of this study are that neoadjuvant pembrolizumab (vs. placebo) in combination with NAC, followed by surgery and adjuvant pembrolizumab (vs. placebo) will improve: 1) event free survival (EFS) by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1); and 2) overall survival (OS).

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Biological: Pembrolizumab Drug: Placebo Drug: Cisplatin Drug: Gemcitabine Drug: Pemetrexed	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

786 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase III, Randomized, Double-blind Trial of Platinum Doublet Chemotherapy +/-Pembrolizumab (MK-3475) as Neoadjuvant/Adjuvant Therapy for Participants With Resectable Stage II, IIIA, and Resectable IIIB (T3-4N2) Non-small Cell Lung Cancer (NSCLC) (KEYNOTE-671)

Actual Study Start Date :

Apr 24, 2018

Anticipated Primary Completion Date :

Jan 20, 2024

Anticipated Study Completion Date :

Jun 29, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NAC + Neoadjuvant/Adjuvant Pembrolizumab Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, intravenous (IV); given on cycle day 1] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, IV; given on cycle day 1].	Biological: Pembrolizumab 200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1. Other Names: KEYTRUDA® MK-3475 Drug: Cisplatin 75 mg/m^2 by IV infusion Q3W, given on cycle day 1. Other Names: PLATINOL® Drug: Gemcitabine 1000 mg/m^2 by IV infusion Q3W, given on cycle days 1 and 8. Given only to participants with squamous NSCLC. Other Names: GEMZAR® Drug: Pemetrexed 500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC. Other Names: Alimta®
Placebo Comparator: NAC + Neoadjuvant/Adjuvant Placebo Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1] in combination with platinum doublet NAC, consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1].	Drug: Placebo Normal saline by IV infusion Q3W, given on cycle day 1. Drug: Cisplatin 75 mg/m^2 by IV infusion Q3W, given on cycle day 1. Other Names: PLATINOL® Drug: Gemcitabine 1000 mg/m^2 by IV infusion Q3W, given on cycle days 1 and 8. Given only to participants with squamous NSCLC. Other Names: GEMZAR® Drug: Pemetrexed 500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC. Other Names: Alimta®

Arm

Intervention/Treatment

Experimental: NAC + Neoadjuvant/Adjuvant Pembrolizumab

Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, intravenous (IV); given on cycle day 1] in combination with platinum doublet neoadjuvant chemotherapy (NAC), consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of pembrolizumab [200 mg, IV; given on cycle day 1].

Biological: Pembrolizumab

200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.

Other Names:

KEYTRUDA®

MK-3475

Drug: Cisplatin

75 mg/m^2 by IV infusion Q3W, given on cycle day 1.

Other Names:

PLATINOL®

Drug: Gemcitabine

1000 mg/m^2 by IV infusion Q3W, given on cycle days 1 and 8. Given only to participants with squamous NSCLC.

Other Names:

GEMZAR®

Drug: Pemetrexed

500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.

Other Names:

Alimta®

Placebo Comparator: NAC + Neoadjuvant/Adjuvant Placebo

Neoadjuvant: Prior to surgery, participants receive up to 4 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1] in combination with platinum doublet NAC, consisting of cisplatin [75 mg/m^2, IV; given on cycle day 1] and either Gemcitabine [1000 mg/m^2, IV; given on cycle days 1 and 8] or Pemetrexed [500 mg/m^2, IV; given on cycle day 1]. Adjuvant: 4-12 weeks following surgery, participants receive 13 cycles (cycle length: 3 weeks) of placebo [normal saline, IV; given on cycle day 1].

Drug: Placebo

Normal saline by IV infusion Q3W, given on cycle day 1.

Drug: Cisplatin

75 mg/m^2 by IV infusion Q3W, given on cycle day 1.

Other Names:

PLATINOL®

Drug: Gemcitabine

1000 mg/m^2 by IV infusion Q3W, given on cycle days 1 and 8. Given only to participants with squamous NSCLC.

Other Names:

GEMZAR®

Drug: Pemetrexed

500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.

Other Names:

Alimta®

Outcome Measures

Primary Outcome Measures

Event Free Survival (EFS) [Up to approximately 5 years]
EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. EFS determined either by biopsy assessed by local pathologist or by investigator-assessed imaging using RECIST 1.1.
Overall Survival (OS) [Up to approximately 5 years]
OS is defined as the time from randomization until death from any cause.

Secondary Outcome Measures

Major Pathological Response (mPR) Rate [Up to approximately 7 weeks following completion of neoadjuvant treatment (up to Study Week 20)]
mPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy.
Pathological Complete Response (pCR) Rate [Up to approximately 7 weeks following completion of neoadjuvant treatment (up to Study Week 20)]
pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.
Global Health Status/Quality of Life (GHS/QoL) Score using the European Organization for Research and Treatment (EORTC) QoL Questionnaire (QLQ-C30) [Baseline (cycle 1 in neoadjuvant phase) and end of follow-up (up to approximately 5 years)]
Change from baseline in GHS/QoL score using the EORTC QLQ-C30 will be determined. The EORTC QLQ-C30 is the most widely used cancer-specific, health-related QoL instrument comprised of 30 individual items arranged as both multi-item scales and individual items. Specifically, these items are divided into 5 functional scales (15 items total), 3 symptom scales (7 items total), 6 individual items, and a GHS/QoL scale composed of 2 items: GHS and QoL. The GHS/QoL score measured here refers to only the composite score calculated for the GHS/QoL scale. Both items on the GHS/QoL scale are scored from 1 (very poor GHS/QoL) to 7 (excellent GHS/QoL) and scores for both items are averaged and a linear transformation applied to standardize the overall GHS/QoL score from 0 to 100, with higher overall scores indicating higher GHS/QoL.
Adverse Events (AEs) [Up to approximately 71 weeks]
The number of participants experiencing an AE will be assessed. 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.
Perioperative Complications [Up to approximately 51 weeks following surgery]
The number of participants experiencing perioperative complications will be assessed. Perioperative complications are a discrete set of both intraoperative and postoperative complications, potentially contributing to increased length of inpatient care and/or delay of adjuvant therapy.
Treatment Discontinuations Due to AEs [Up to approximately 57 weeks]
The number of participants discontinuing study therapy due to an AE will be assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Have previously untreated and pathologically confirmed resectable Stage II, IIIA, or IIIB (N2) NSCLC.
Be able to undergo protocol therapy, including necessary surgery. A positron emission tomography (PET) scan may be utilized as a surrogate for pathologic staging of N1 lymph nodes for participants with T2b and T4 tumors.
If male, must agree to use contraception or practice abstinence as well as refrain from donating sperm during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention.
If female, may participate if not pregnant or breastfeeding, and at least one of the following conditions apply: 1) not a woman of childbearing potential (WOCBP); or 2) a WOCBP who agrees to follow contraceptive guidance during the treatment period and for the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
Have available formalin-fixed paraffin embedded (FFPE) tumor tissue sample blocks for submission. If blocks are not available, have unstained slides for submission for central programmed death-ligand 1 (PD-L1) testing.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days of randomization.
Have adequate organ function.

Exclusion Criteria:

Has one of the following tumor locations/types:1) NSCLC involving the superior sulcus;

Large cell neuro-endocrine cancer (LCNEC); or 3) Sarcomatoid tumor.

Has a history of (non-infectious) pneumonitis /interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease that requires steroids.
Has an active infection requiring systemic therapy.
Has had an allogenic tissue/sold organ transplant.
Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients.
Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
Has an active autoimmune disease that has required systemic treatment in past 2 years.
Has a known history of human immunodeficiency virus (HIV) infection.
Has a known history of Hepatitis B or Hepatitis C.
Has a known history of active tuberculosis.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate.
Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor.
Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy prior to randomization/allocation.
Has received prior radiotherapy within 2 weeks of start of trial treatment.
Has received a live vaccine within 30 days prior to the first dose of trial drug.
Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
Has a diagnosis of immunodeficiency or is receiving either systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center ( Site 0028)	Gilbert	Arizona	United States	85234
2	Western Regional Medical Center, Inc. ( Site 0050)	Goodyear	Arizona	United States	85338
3	University of Arizona Cancer Center - Dignity Health ( Site 0062)	Phoenix	Arizona	United States	85004
4	University of Arizona Cancer Center ( Site 0012)	Tucson	Arizona	United States	85724
5	Pacific Cancer Medical Center, Inc. ( Site 0004)	Anaheim	California	United States	92801
6	Providence Saint Joseph Medical Center ( Site 0061)	Burbank	California	United States	91505
7	Pacific Cancer Care ( Site 0035)	Monterey	California	United States	93940
8	John Wayne Cancer Institute ( Site 0049)	Santa Monica	California	United States	90404
9	St Joseph Heritage Healthcare ( Site 0040)	Santa Rosa	California	United States	95403
10	Stanford University, Stanford Cancer Center ( Site 0046)	Stanford	California	United States	94305
11	Hartford Hospital ( Site 0069)	Hartford	Connecticut	United States	06102
12	Helen F. Graham Cancer Center & Research Institute ( Site 0015)	Newark	Delaware	United States	19718
13	Mayo Clinic Jacksonville ( Site 0022)	Jacksonville	Florida	United States	32224
14	Miami Cancer Institute-Baptist Hospital ( Site 0068)	Miami	Florida	United States	33176
15	Southeastern Regional Medical Center ( Site 0051)	Newnan	Georgia	United States	30265
16	Northwest Oncology and Hematology ( Site 0001)	Elk Grove Village	Illinois	United States	60007
17	Ingalls Memorial Hospital ( Site 0044)	Harvey	Illinois	United States	60426
18	PPG-Oncology ( Site 0043)	Fort Wayne	Indiana	United States	46845
19	University of Iowa Hospital and Clinics ( Site 0010)	Iowa City	Iowa	United States	52242
20	Ashland-Bellefonte Cancer Center ( Site 0021)	Ashland	Kentucky	United States	41101
21	Harry & Jeanette Weinberg Cancer Institute ( Site 0081)	Baltimore	Maryland	United States	21237
22	Boston Medical Center ( Site 0057)	Boston	Massachusetts	United States	02118
23	UMass Memorial Medical Center ( Site 0030)	Worcester	Massachusetts	United States	01655
24	Henry Ford Health System ( Site 0031)	Detroit	Michigan	United States	48202
25	Herbert Herman Cancer Center, Sparrow Hospital ( Site 0034)	Lansing	Michigan	United States	48912
26	Mayo Clinic ( Site 0026)	Rochester	Minnesota	United States	55905
27	St. Vincent Healthcare Frontier Cancer Center ( Site 0005)	Billings	Montana	United States	59102
28	University of Nebraska Medical Center ( Site 0047)	Omaha	Nebraska	United States	68198-7680
29	Memorial Sloan Kettering Cancer Center Basking Ridge ( Site 0074)	Basking Ridge	New Jersey	United States	07920
30	Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0077)	Middletown	New Jersey	United States	07748
31	MSKCC-Bergen ( Site 0075)	Montvale	New Jersey	United States	07645
32	St. Peter's Hospital Cancer Care Center ( Site 0039)	Albany	New York	United States	12208
33	Montefiore Einstein Center ( Site 0016)	Bronx	New York	United States	10461
34	Memorial Sloan-Kettering Cancer Center at Commack ( Site 0076)	Commack	New York	United States	11725
35	Memorial Sloan Kettering Cancer Center Westchester ( Site 0079)	Harrison	New York	United States	10604
36	Memorial Sloan Kettering Cancer Center ( Site 0060)	New York	New York	United States	10065
37	Stony Brook University Medical Center - Cancer Center ( Site 0019)	Stony Brook	New York	United States	11794-9447
38	Memorial Sloan Kettering Cancer Center - Nassau ( Site 0078)	Uniondale	New York	United States	11553
39	White Plains Hospital Center for Cancer Care ( Site 0007)	White Plains	New York	United States	10601
40	Southwestern Regional Medical Center, Inc. ( Site 0054)	Tulsa	Oklahoma	United States	74133
41	OHSU Center for Health & Healing ( Site 1006)	Portland	Oregon	United States	97239
42	UPMC Pinnacle Health System - East Location ( Site 0063)	Harrisburg	Pennsylvania	United States	17109
43	Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0053)	Philadelphia	Pennsylvania	United States	19124
44	Allegheny General Hospital ( Site 0009)	Pittsburgh	Pennsylvania	United States	15212
45	UPMC Hillman Cancer Centers ( Site 0041)	Pittsburgh	Pennsylvania	United States	15232
46	VA Pittsburgh Healthcare System ( Site 0052)	Pittsburgh	Pennsylvania	United States	15240
47	Saint Francis Cancer Center ( Site 0096)	Greenville	South Carolina	United States	29607
48	Emily Couric Clinical Cancer Center ( Site 0013)	Charlottesville	Virginia	United States	22903
49	Inova Schar Cancer Institute ( Site 0032)	Fairfax	Virginia	United States	22031
50	Virginia Cancer Specialists, PC ( Site 0080)	Fairfax	Virginia	United States	22031
51	Providence Regional Cancer Partnership ( Site 0065)	Everett	Washington	United States	98201
52	Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0136)	Berazategui	Buenos Aires	Argentina	B1884BBF
53	Hospital Privado de Comunidad. ( Site 0130)	Mar del Plata	Buenos Aires	Argentina	B7602CBM
54	Hospital Universitario Austral ( Site 0127)	Pilar	Buenos Aires	Argentina	B1629ODT
55	Fundacion Favaloro ( Site 0128)	Ciudad de Buenos Aires	Caba	Argentina	C1093AAS
56	Sanatorio Britanico ( Site 0125)	Rosario	Santa Fe	Argentina	S2000CVB
57	Sanatorio Parque ( Site 0135)	Rosario	Santa Fe	Argentina	S2000DSV
58	Hospital Provincial del Centenario ( Site 0131)	Rosario	Santa Fe	Argentina	S2002KDS
59	Hospital Privado Universitario de Córdoba ( Site 0139)	Cordoba		Argentina	5016
60	Sanatorio Allende ( Site 0129)	Cordoba		Argentina	X5000JHQ
61	CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0133)	San Juan		Argentina	J5402DIL
62	Orange Health Services ( Site 0624)	Orange	New South Wales	Australia	2800
63	Westmead Hospital ( Site 0621)	Westmead	New South Wales	Australia	2145
64	AZ Sint-Maarten ( Site 0226)	Mechelen	Antwerpen	Belgium	2800
65	Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman ( Site 0223)	Liège	Liege	Belgium	4000
66	UZ Gent ( Site 0224)	Gent	Oost-Vlaanderen	Belgium	9000
67	AZ Nikolaas ( Site 0225)	Sint-Niklaas	Oost-Vlaanderen	Belgium	9100
68	UZ Leuven ( Site 0221)	Leuven	Vlaams-Brabant	Belgium	3000
69	AZ Delta ( Site 0222)	Roeselare	West-Vlaanderen	Belgium	8800
70	Centro Regional Integrado de Oncologia ( Site 0160)	Fortaleza	Ceara	Brazil	60336-232
71	Instituto do Cancer do Ceara ( Site 0152)	Fortaleza	Ceara	Brazil	60430-230
72	Sirio-Libanes Brasilia - Centro de Oncologia - Asa Sul ( Site 0159)	Brasilia	Distrito Federal	Brazil	70200-730
73	Liga Norte Riograndense Contra o Cancer ( Site 0150)	Natal	Rio Grande Do Norte	Brazil	59075-740
74	Hospital de Caridade de Ijui ( Site 0153)	Ijui	Rio Grande Do Sul	Brazil	98700 000
75	Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0146)	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
76	Hospital Nossa Senhora da Conceicao ( Site 0145)	Porto Alegre	Rio Grande Do Sul	Brazil	91350-200
77	YNOVA Pesquisa Clinica ( Site 0823)	Florianopolis	Santa Catarina	Brazil	88020-210
78	Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0144)	Barretos	Sao Paulo	Brazil	14784-400
79	Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0149)	Rio de Janeiro		Brazil	20230-130
80	Hospital Paulistano - Amil Clinical Research ( Site 0822)	Sao Paulo		Brazil	01321-001
81	Hospital Alemao Oswaldo Cruz ( Site 0158)	Sao Paulo		Brazil	01327-001
82	Princess Margaret Cancer Centre ( Site 0109)	Toronto	Ontario	Canada	M5G 2M9
83	CIUSSS du Saguenay-Lac-St-Jean ( Site 0101)	Chicoutimi	Quebec	Canada	G7H 5H6
84	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0110)	Montreal	Quebec	Canada	H2X 0C1
85	CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0104)	Montreal	Quebec	Canada	H3T 1M5
86	McGill University Health Centre ( Site 0111)	Montreal	Quebec	Canada	H4A 3J1
87	Tianjin Medical University General Hospital ( Site 0806)	Tianjin	Anhui	China	300052
88	Beijing Cancer Hospital ( Site 0810)	Beijing	Beijing	China	100010
89	Beijing Cancer Hospital ( Site 0811)	Beijing	Beijing	China	100010
90	Cancer Hospital Chinese Academy of Medical Sciences ( Site 0801)	Beijing	Beijing	China	100021
91	Peking University Third Hospital ( Site 0812)	Beijing	Beijing	China	100191
92	Peking Union Medical College Hospital ( Site 0809)	Beijing	Beijing	China	100730
93	Sun Yat-Sen University Cancer Center ( Site 0816)	Guangzhou	Guangdong	China	510060
94	Hunan Cancer Hospital ( Site 0815)	Changsha	Hunan	China	410013
95	Fudan University Shanghai Cancer Center ( Site 0813)	Shanghai	Shanghai	China	200032
96	Zhongshan Hospital of Fudan University ( Site 0808)	Shanghai	Shanghai	China	200032
97	Shanghai Pulmonary Hospital-Thoracic Surgery department ( Site 0817)	Shanghai	Shanghai	China	200433
98	Tang Du Hospital ( Site 0803)	XI An	Shanxi	China	710038
99	The First Affiliated Hospital of Zhejiang University ( Site 0804)	Hangzhou	Zhejiang	China	310003
100	Zhejiang Cancer Hospital.... ( Site 0814)	Hangzhou	Zhejiang	China	310022
101	Hwa Mei Hospital University of Chinese Academy of Sciences ( Site 0802)	Ningbo	Zhejiang	China	315010
102	SA Pohja-Eesti Regionaalhaigla ( Site 1100)	Tallinn	Harjumaa	Estonia	13419
103	Hopital Foch ( Site 0243)	Suresnes	Ain	France	92150
104	Nouvel Hopital Civil ( Site 0255)	Strasbourg	Bas-Rhin	France	67091
105	CHU de Toulouse - Hopital Larrey ( Site 0258)	Toulouse	Haute-Garonne	France	31100
106	Clinique Francois Chenieux ( Site 0246)	Limoges	Haute-Vienne	France	87039
107	Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 0241)	Pierre-Benite	Rhone-Alpes	France	69310
108	Centre Hospitalier Metropole Savoie Site de Chambery ( Site 0245)	Chambery	Savoie	France	73011
109	Centre Hospitalier Annecy Genevois ( Site 0242)	Pringy	Savoie	France	74374
110	CHU de Rouen ( Site 0252)	Rouen	Seine-Maritime	France	76031
111	Hôpital Avicenne - Service d oncologie medicale ( Site 0249)	Bobigny	Seine-Saint-Denis	France	93000
112	H.I.A. Sainte-Anne ( Site 0251)	Toulon	Var	France	83800
113	Institut Curie ( Site 0250)	Paris		France	75248
114	Klinikum Esslingen GmbH ( Site 0875)	Esslingen	Baden-Wurttemberg	Germany	73730
115	LKI Lungenfachklinik Immenhausen ( Site 0268)	Immenhausen	Hessen	Germany	34376
116	Florence Nightingale Krankenhaus ( Site 0874)	Duesseldorf	Nordrhein-Westfalen	Germany	40489
117	Lungenklinik Hemer ( Site 0269)	Hemer	Nordrhein-Westfalen	Germany	58675
118	Mathias Spital Rheine ( Site 0261)	Rheine	Nordrhein-Westfalen	Germany	48431
119	Katholisches Klinikum Koblenz Haus Marienhof ( Site 0873)	Koblenz	Rheinland-Pfalz	Germany	56073
120	Universitaetsklinikum Carl Gustav Carus ( Site 0273)	Dresden	Sachsen	Germany	01307
121	Universitaetsklinikum Leipzig AOeR ( Site 0277)	Leipzig	Sachsen	Germany	04103
122	LungenClinic Grosshansdorf GmbH ( Site 0267)	Grosshansdorf	Schleswig-Holstein	Germany	22927
123	Universitaetsklinikum Schleswig Holstein ( Site 0871)	Kiel	Schleswig-Holstein	Germany	24105
124	Zentralklinik Bad Berka GmbH ( Site 0264)	Bad Berka	Thuringen	Germany	99437
125	SRH Waldklinikum Gera GmbH ( Site 0272)	Gera	Thuringen	Germany	07548
126	Evangelische Lungenklinik Berlin ( Site 0274)	Berlin		Germany	13125
127	HELIOS Klinikum Emil von Behring ( Site 0280)	Berlin		Germany	14165
128	Asklepios Klinikum Hamburg ( Site 0271)	Hamburg		Germany	21075
129	Cork University Hospital ( Site 0452)	Wilton	Cork	Ireland
130	St James Hospital ( Site 0451)	Dublin		Ireland	D08 K0Y5
131	Mid Western Cancer Centre ( Site 0450)	Limerick		Ireland	V98F858
132	Istituto Nazionale Tumori ( Site 0309)	Milano	Abruzzo	Italy	20133
133	Azienda Ospedaliera dei Colli V. Monaldi ( Site 0301)	Napoli	Campania	Italy	80131
134	IRST-Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori ( Site 0300)	Meldola	Forli-Cesena	Italy	47014
135	Istituto Clinico Humanitas Research Hospital ( Site 0314)	Rozzano	Lombardia	Italy	20089
136	ASST Grande Ospedale Metropolitano Niguarda-Oncologia Falck ( Site 0315)	Milan	Milano	Italy	20162
137	Azienda Ospedaliera San Gerardo ( Site 0308)	Monza	Monza E Brianza	Italy	20900
138	AOU San Luigi Gonzaga di Orbassano ( Site 0313)	Orbassano	Torino	Italy	10043
139	Azienda Ospedaliera Spedali Civili di Brescia ( Site 0307)	Brescia		Italy	25123
140	IRCCS Ospedale San Raffaele di Milano ( Site 0303)	Milano		Italy	20132
141	Azienda Ospedaliera San Camillo Forlanini ( Site 0311)	Roma		Italy	00152
142	Aichi Cancer Center Hospital ( Site 0765)	Nagoya	Aichi	Japan	464-8681
143	National Cancer Center Hospital East ( Site 0761)	Kashiwa	Chiba	Japan	277-8577
144	HP of the Univ. of Occupational and Environmental Health, Japan ( Site 0770)	Kitakyushu	Fukuoka	Japan	807-8556
145	Hyogo Cancer Center ( Site 0764)	Akashi	Hyogo	Japan	673-8558
146	St. Marianna University School of Medicine Hospital ( Site 0769)	Kawasaki	Kanagawa	Japan	216-8511
147	Kanagawa Cancer Center ( Site 0763)	Yokohama	Kanagawa	Japan	241-8515
148	Oita University Hospital ( Site 0766)	Yufu	Oita	Japan	879-5593
149	Fukushima Medical University Hospital ( Site 0772)	Fukushima		Japan	960-1295
150	Hiroshima University Hospital ( Site 0762)	Hiroshima		Japan	734-8551
151	National Cancer Center Hospital ( Site 0767)	Tokyo		Japan	104-0045
152	Juntendo University Hospital ( Site 0768)	Tokyo		Japan	113-8431
153	Tokyo Medical University Hospital ( Site 0771)	Tokyo		Japan	160-0023
154	National Cancer Center ( Site 0702)	Gyeonggi-do	Kyonggi-do	Korea, Republic of	10408
155	The Catholic University of Korea St. Vincent s Hospital ( Site 0705)	Gyeonggi-do	Kyonggi-do	Korea, Republic of	16247
156	Asan Medical Center ( Site 0701)	Seoul		Korea, Republic of	05505
157	Samsung Medical Center ( Site 0704)	Seoul		Korea, Republic of	06351
158	SMG-SNU Boramae Medical Center ( Site 0707)	Seoul		Korea, Republic of	07071
159	Pauls Stradins Clinical University Hospital ( Site 0911)	Riga		Latvia	1002
160	Riga East Clinical University Hospital ( Site 0912)	Riga		Latvia	1079
161	LSMUL Kauno Klinikos ( Site 0932)	Kaunas		Lithuania	50161
162	Nacionalinis Vezio Institutas ( Site 0931)	Vilnius		Lithuania	08406
163	Sarawak General Hospital ( Site 0782)	Kuching	Sarawak	Malaysia	93586
164	University Malaya Medical Centre ( Site 0781)	Kuala Lumpur		Malaysia	59100
165	Centrum Pulmonologii i Torakochirurgii w Bystrej ( Site 0484)	Bystra	Dolnoslaskie	Poland	43-360
166	Dolnoslaskie Centrum Onkologii. ( Site 0491)	Wroclaw	Dolnoslaskie	Poland	53-413
167	Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 0488)	Bydgoszcz	Kujawsko-pomorskie	Poland	85-796
168	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi ( Site 0493)	Lodz	Lodzkie	Poland	93-513
169	Szpital Specjalistyczny w Prabutach Sp. z o.o. ( Site 0483)	Prabuty	Pomorskie	Poland	82-550
170	Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0487)	Poznan	Wielkopolskie	Poland	60-569
171	S C Pelican Impex SRL ( Site 0506)	Oradea	Bihor	Romania	410450
172	Centrul Medical Medicover Victoria ( Site 0514)	Bucharest	Bucuresti	Romania	010626
173	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0501)	Cluj Napoca	Cluj	Romania	400015
174	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0515)	Cluj-Napoca	Cluj	Romania	400015
175	SC Radiotherapy Center Cluj SRL ( Site 0509)	Comuna Floresti	Cluj	Romania	407280
176	S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0504)	Craiova	Dolj	Romania	200347
177	S.C.R.T.C.Radiology Therapeutic Center SRL ( Site 0511)	Otopeni	Ilfov	Romania	075100
178	S C Oncocenter Oncologie Medicala S R L ( Site 0505)	Timisoara	Timis	Romania	300166
179	Spitalul Sf. Constantin ( Site 0512)	Brasov		Romania	500091
180	Euroclinic Hospital Bucharest ( Site 0510)	Bucuresti		Romania	014461
181	S.C.Focus Lab Plus S.R.L ( Site 0513)	Bucuresti		Romania	021389
182	Spitalul clinic Judetean de urgenta Constanta ( Site 0508)	Constanta		Romania	900591
183	Spitalul Judetean de Urgenta .Sf. Ioan cel Nou. ( Site 0503)	Suceava		Romania	720237
184	Chelyabinsk Regional Clinical Oncological Dispensary ( Site 0530)	Chelyabinsk	Chelyabinskaya Oblast	Russian Federation	454087
185	N.N. Blokhin NMRCO ( Site 0521)	Moscow	Moskva	Russian Federation	115478
186	National Medical Research Radiology Centre ( Site 0535)	Moscow	Moskva	Russian Federation	125284
187	Medical Rehabilitation Center ( Site 0534)	Moscow	Moskva	Russian Federation	125367
188	SBHI Leningrad Regional Clinical Hospital ( Site 0524)	Saint Petersburg	Sankt-Peterburg	Russian Federation	194291
189	Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0533)	Saint Petersburg	Sankt-Peterburg	Russian Federation	197758
190	Municipal Clinical Oncology Center ( Site 0523)	Saint Petersburg	Sankt-Peterburg	Russian Federation	198255
191	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0529)	Kazan	Tatarstan, Respublika	Russian Federation	420029
192	Tomsk Scientific Research Institute of Oncology ( Site 0526)	Tomsk	Tomskaya Oblast	Russian Federation	634028
193	Wits Clinical Research ( Site 0570)	Parktown-Johannesburg	Gauteng	South Africa	2193
194	Wilgers Oncology Centre ( Site 0573)	Pretoria	Gauteng	South Africa	0081
195	The Oncology Centre ( Site 0571)	Durban	Kwazulu-Natal	South Africa	4001
196	Cape Town Oncology Trials Pty Ltd ( Site 0572)	Kraaifontein	Western Cape	South Africa	7570
197	Hospital Germans Trias i Pujol. ICO de Badalona ( Site 0381)	Badalona	Barcelona	Spain	08916
198	Instituto Catalan de Oncologia - ICO ( Site 0388)	L Hospitalet De Llobregat	Barcelona	Spain	08908
199	Hospital Universitario de Girona Doctor Josep Trueta ( Site 0386)	Girona	La Coruna	Spain	17007
200	Hospital Universitario Insular de Gran Canaria ( Site 0383)	Las Palmas de Gran Canaria	Las Palmas	Spain	35001
201	Hospital de la Santa Creu i Sant Pau ( Site 0385)	Barcelona		Spain	08025
202	Hospital Universitari Vall d Hebron ( Site 0389)	Barcelona		Spain	08035
203	Hospital General Universitario Gregorio Maranon ( Site 0382)	Madrid		Spain	28009
204	Hospital Virgen del Rocio ( Site 0387)	Sevilla		Spain	41013
205	Kaohsiung Chang Gung Memorial Hospital ( Site 0725)	Kaohsiung		Taiwan	83301
206	China Medical University Hospital ( Site 0724)	Taichung		Taiwan	40447
207	National Taiwan University Hospital ( Site 0721)	Taipei		Taiwan	10048
208	Taipei Veterans General Hospital ( Site 0722)	Taipei		Taiwan	112
209	Tri-Service General Hospital ( Site 0726)	Taipei		Taiwan	114
210	Chang Gung Medical Foundation.Linkou Branch ( Site 0723)	Taoyuan		Taiwan	333
211	Cherkassy Regional Oncological Center ( Site 0613)	Cherkasy	Cherkaska Oblast	Ukraine	18009
212	City Clinical Hosp.4 of DCC ( Site 0607)	Dnipro	Dnipropetrovska Oblast	Ukraine	49102
213	MI Precarpathian Clinical Oncology Center ( Site 0603)	Ivano-Frankivsk	Ivano-Frankivska Oblast	Ukraine	76018
214	MI KhRC Kherson Regional Oncology Dispensary ( Site 0614)	Kherson	Khersonska Oblast	Ukraine	73000
215	PP PPC Acinus Medical and Diagnostic Centre ( Site 0609)	Kropyvnytsky	Kirovohradska Oblast	Ukraine	25006
216	National Cancer Institute of the MoH of Ukraine ( Site 0605)	Kyiv	Kyivska Oblast	Ukraine	03022
217	Kyiv City Clinical Oncological Center ( Site 0601)	Kyiv	Kyivska Oblast	Ukraine	03115
218	MI Odessa Regional Oncological Centre ( Site 0608)	Odesa	Odeska Oblast	Ukraine	65055
219	Zaporizhzhya Regional Clinical Oncology Center ( Site 0606)	Zaporizhzhya	Zaporizka Oblast	Ukraine	69040
220	Leicester Royal Infirmary ( Site 0447)	Leicester	Leicestershire	United Kingdom	LE1 5WW
221	The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0456)	Wirral	Liverpool	United Kingdom	CH63 4JY
222	Royal Marsden NHS Foundation Trust ( Site 0458)	London	London, City Of	United Kingdom	SW3 6JJ
223	Royal Marsden Hospital ( Site 0457)	Sutton	London, City Of	United Kingdom	SM2 5PT
224	Nottingham City Hospital Campus ( Site 0441)	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
225	Heartlands Hospital in Birmingham ( Site 0455)	Birmingham		United Kingdom	B9 5SS
226	Freeman Hospital ( Site 0444)	Newcastle upon Tyne		United Kingdom	NE7 7DN
227	Plymouth Hospitals NHS Trust ( Site 0443)	Plymouth		United Kingdom	PL6 8DH