NAVIGATE: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors

Sponsor

Bayer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02576431

Collaborator

(none)

204

Enrollment

159

Locations

Arms

119

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib is a drug that blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors Harboring NTRK Fusion	Drug: BAY2757556 (Larotrectinib, Vitrakvi)	Phase 2

Detailed Description

The primary objective of this study is to investigate the efficacy of larotrectinib for the treatment of advanced solid tumors harboring a fusion of neurotrophic tyrosine receptor kinase (NTRK) of types 1-3 in children and adults.

Secondary objectives comprise the efficacy and safety of larotrectinib in different NTRK-tumor types.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

204 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Basket Study of the Oral TRK Inhibitor Larotrectinib in Subjects With NTRK Fusion-positive Tumors

Actual Study Start Date :

Sep 30, 2015

Anticipated Primary Completion Date :

Aug 15, 2023

Anticipated Study Completion Date :

Aug 29, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1_NSCLC Patients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 2_Thyroid Patients with solid thyroid tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 3_Sarcoma Patients with soft-tissue sarcoma harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 4_Colorectal Patients with solid colorectal tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 5_Salivary Patients with solid salivary tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 6_Biliary Patients with solid biliary tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 7_Primary CNS Patients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 8_Other tumors Patients with e.g. kidney cancer, squamous cell cancer of head or neck or ovarian solid tumors harboring NTRK fusions (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 9_Solid tumors without confirmed NTRK fusion Patients eligible for arms 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the sponsor at the time of consent (arm closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 10- Prospective cohort Patients with melanoma, non secretory breast and colorectal cancer or other tumor types harboring NTRK fusions, except soft tissue sarcoma, salivary gland and thyroid cancer (closed)	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101
Experimental: Arm 11_Bone health cohort Patients with all tumor types harboring NTRK fusions, not eligible for the main prospective cohort, including patients with non-measurable disease	Drug: BAY2757556 (Larotrectinib, Vitrakvi) Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles. Other Names: LOXO-101

Outcome Measures

Primary Outcome Measures

Best overall response rate by IRC [Up to 120 months]
Proportion of subjects with either complete response or partial response as determined by an independent radiology committee (IRC) using RECIST or RANO criteria.

Secondary Outcome Measures

Best overall response rate by investigator [Up to 120 months]
Proportion of subjects with either complete response or partial response as determined by the treating investigator using RECIST or RANO criteria.
Duration of response (DOR) by IRC [Up to 120 months]
Duration of response is the number of months from the start of confirmed complete response or partial response to disease progression or death. Complete response, partial response and disease progression are assessed by an independent radiology committee (IRC).
Duration of response (DOR) by investigator [Up to 120 months]
Duration of response is the number of months from the start of confirmed complete response or partial response to disease progression or death. Complete response, partial response and disease progression are assessed by the treating investigator.
Clinical benefit rate (CBR) [Up to 120 months]
Proportion of subjects with best overall response of complete response, partial response or stable disease lasting 16 or more weeks following the initiation of larotrectinib.
Progression-free survival (PFS) after Larotrectinib [Up to 120 months]
Number of months from initiation of larotrectinib to either disease progression or death due to any cause.
Overall survival time [Up to 120 months]
Number of months from the initiation of larotrectinib to the date of death due to any cause.
Progression-free survival (PFS) after past cancer therapy [Up to 120 months]
Number of months from initiation of the line of therapy preceding larotrectinib to either disease progression or death due to any cause.
Number of subjects with adverse events [Up to 120 months]
Number of subjects with serious adverse events [Up to 120 months]
Number of subjects with treatment-related adverse events [Up to 120 months]
Severity of adverse events [Up to 120 months]
Severity of serious adverse events [Up to 120 months]
Severity of treatment-related adverse events [Up to 120 months]
Duration of adverse events [Up to 120 months]
Duration of serious adverse events [Up to 120 months]
Duration of treatment-related adverse events [Up to 120 months]
Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration [Up to 120 months]
Severity of safety-relevant changes in clinical parameters or vital signs after drug administration [Up to 120 months]
Proportion of patients with any tumor regression (i.e., measured as shrinkage of target lesions) as a best response [Up to 120 months]
Concordance coefficient [Up to 120 months]
Concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor with the diagnostic test being evaluated by the Sponsor

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) or other similarly-certified laboratories.
Subjects who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments and in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
Subjects must have at least one measurable lesion as defined by RECIST v1.1. Subjects with solid tumors without RECIST v1.1 measurable disease (e.g., evaluable disease only) had been eligible for enrollment to Cohort 8 as per protocol versions 1.0 - 8.0, regardless of tumor type. Subjects with primary CNS tumors should meet the following criteria

Have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to C1D1 of therapy, as recommended or appropriate for that CNS tumor type.
Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice.
Imaging study performed within 28 days before enrollment. If on steroid therapy, the dose must be stable for at least 7 days immediately before and during the imaging study.
Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.

For subjects eligible for enrollment to bone health cohort, inclusion criterion 3 is modified as the following:

Subjects must have at least one lesion at baseline (measurable or non-measurable as defined by RECIST v1.1 or RANO criteria, as appropriate to tumor type).
Subjects with primary CNS tumors must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.

Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) ≥50%
Tumor tissue before treatment (mandatory). If neither fresh tissue can be obtained nor archival tissue is available patients might be enrolled after consultation with the sponsor.
Willingness of men and women of reproductive potential to use double effective birth control methods, defined as one used by the subject and another by his/her partner, for the duration of treatment and for 1 month following study completion.
For subjects eligible for enrollment to bone health cohort only: life expectancy of at least 6 months, based on investigator assessment.

Exclusion Criteria:

Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting tropomyosin receptor kinase (TRK). Subjects who received less than 28 days of treatment and discontinued because of intolerance or toxicity are eligible.
Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain metastases are eligible to participate in the study.) Subjects with primary central nervous system (CNS) tumors are eligible.
Pregnancy or lactation.
Active uncontrolled systemic bacterial, viral, or fungal infection Common Terminology Criteria for Adverse Events(CTCAE) grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures.
Unstable cardiovascular disease is defined as:
In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy.
Myocardial infarction within 3 months of screening.
Stroke within 3 months of screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Center	Palo Alto	California	United States	94304
2	UCLA-Santa Monica Medical Center	Santa Monica	California	United States	90404
3	Memorial Hospital West	Pembroke	Florida	United States	33028
4	University of Chicago	Chicago	Illinois	United States	60637
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
7	Dartmouth Hitchock Medical Center	Lebanon	New Hampshire	United States	03756
8	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
9	University of North Carolina Hospitals	Chapel Hill	North Carolina	United States	27599
10	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157-1082
11	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195-0002
12	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
13	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
14	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
15	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
16	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
17	Inova Schar Cancer Institute	Fairfax	Virginia	United States	22031
18	University of Washington	Seattle	Washington	United States	98109
19	West Virginia University	Morgantown	West Virginia	United States	26505
20	Centro Medico Austral	Buenos Aires	Ciudad Auton. De Buenos Aires	Argentina	C1019ABS
21	Hospital Británico	Buenos Aires	Ciudad Auton. De Buenos Aires	Argentina	C1280AEB
22	Instituto Medico Especializado Alexander Fleming	Buenos Aires	Ciudad Auton. De Buenos Aires	Argentina	C1426ANZ
23	Centro Estudios Médicos e Invest. Clínicas "Dr. N. Quirno"	Buenos Aires	Ciudad Auton. De Buenos Aires	Argentina	C1431FWO
24	Hospital Alemán	Buenos Aires	Ciudad Auton. De Buenos Aires	Argentina
25	Fundación Cenit para la Investigación en Neurociencias	Caba	Ciudad Auton. De Buenos Aires	Argentina	C1125 ABD
26	Instituto de Oncología de Rosario	Rosario	Santa Fe	Argentina	S2000KZE
27	Centro Médico San Roque	San Miguel de Tucumán	Tucuman	Argentina	T4000HXU
28	Macquarie University Hospital	Macquarie University	New South Wales	Australia	2109
29	Royal Darwin Hospital	Tiwi	Northern Territory	Australia	0810
30	St John of God Healthcare	Subiaco	Western Australia	Australia	6008
31	Sir Charles Gairdner Hospital	Nedlands		Australia	6009
32	Institut Jules Bordet/Jules Bordet Instituut	Anderlecht		Belgium	1070
33	Hosp. Araujo Jorge da Associação de Combate ao Câncer	Goiânia	Goiás	Brazil	74605-070
34	Cenantron Centro Avançado de Tratamento Oncológico, Ltda.	Belo Horizonte	Minas Gerais	Brazil	30110-090
35	Associação Hospital de Caridade de Ijuí	Ijuí	Rio Grande Do Sul	Brazil	98700-000
36	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90050-170
37	Fundação Pio XII - Hospital de Câncer de Barretos	Barretos	Sao Paulo	Brazil	14784-400
38	Hospital de Base da Fundação F M S J Rio Preto	São José do Rio Preto	Sao Paulo	Brazil	15090-000
39	Instituto do Câncer do Estado de São Paulo	São Paulo	Sao Paulo	Brazil	01246-000
40	Clín. de Pesq. e Centro de Estudos em Onco Gineco Mamária	São Paulo	Sao Paulo	Brazil	01317-000
41	Real e Benemérita Associação Portuguesa de Beneficência	São Paulo	Sao Paulo	Brazil	01323-001
42	IBCC - Instituto Brasileiro de Controle do Cancer	São Paulo	Sao Paulo	Brazil	04014-002
43	Instituto Nacional do Câncer - INCA - HC II	Rio de Janeiro		Brazil	20220-410
44	INCA - Hospital do Cancer III	Rio de Janeiro		Brazil	20560-121
45	Oncoclínicas Rio de Janeiro S.A	Rio de Janeiro		Brazil	22250-905
46	Hospital Sirio Libanes	Sao Paulo		Brazil	01308-050
47	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
48	Juravinski Cancer Centre-McMaster Medical Unit	Hamilton	Ontario	Canada	L8V 5C2
49	London Regional Cancer Program, London Health Sciences Ctr	London	Ontario	Canada	N6A 5W9
50	Sir Mortimer B. Davis Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
51	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510060
52	Sichuan University West China Hospital	Chengdu	Sichuan	China
53	Beijing Cancer Hospital	Beijing		China	100142
54	Zhongshan Hospital, Fudan University	Shanghai		China	200032
55	Instituto Nacional de Cancerología INC Colombia	Bogotá	Cundinamarca	Colombia	111511
56	Oncomédica S.A.	Montería	Córdoba	Colombia	230002
57	Fundación Oftalmológica de Santander Carlos Ardila Lule	Floridablanca	Santander	Colombia	681004
58	Masarykuv onkologicky ustav	Brno		Czechia	65 653
59	Fakultni Nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
60	Fakultni Nemocnice Olomouc	Olomouc		Czechia	775 20
61	Fakultni Thomayerova Nemocnice	Praha 4		Czechia	140 59
62	Finsen Centre	Copenhagen		Denmark	2100
63	Hopital Jean Minjoz	Besancon		France	25030
64	Institut Bergonié - Unicancer Nouvelle Aquitaine	Bordeaux Cedex		France	33076
65	Hôpital Saint André - Bordeaux	Bordeaux		France	33000
66	Centre Léon Bérard	Lyon Cedex		France	39373
67	Centre Antoine Lacassagne	Nice Cedex 2		France	06102
68	Hôpital Saint Louis	Paris		France	75010
69	Hopital Saint Antoine - Paris	Paris		France	75012
70	Hôpital de la Pitié-Salpétrière	Paris		France	75651
71	Centre Hospitalier Lyon Sud	Pierre Benite		France	69495
72	Hôpital de la Milétrie	POITIERS cedex		France	86021
73	Hôpital Guillaume et René Laennec - Nantes	Saint Herblain		France	44093
74	Institut de Cancérologie de l'Ouest - Saint Herblain	Saint Herblain		France	44805
75	ICANS - Institut de Cancérologie de Strasbourg Europe	Strasbourg		France	67033
76	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg	Germany	69120
77	Heinrich-Heine-Universität Düsseldorf	Düsseldorf	Nordrhein-Westfalen	Germany	40225
78	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen	Germany	45122
79	Charité Comprehensive Cancer Center (CCCC)	Berlin		Germany	12203
80	AGIOS SAVVAS Anticancer Hospital of Athens	Athens		Greece	115 22
81	LAIKO General Hospital of Athens	Athens		Greece	11526
82	General Hospital of Athens "ALEXANDRA"	Athens		Greece	11528
83	General Oncology Hospital of Kifissia AGIOI ANARGYROI	Kifissia / Athens		Greece	14564
84	University General Hospital of Patra	Patra		Greece	26504
85	MH Egeszsegugyi Kozpont	Budapest		Hungary	1062
86	Orszagos Onkologiai Intezet	Budapest		Hungary	1122
87	Debreceni Egyetem Klinikai Kozpont	Debrecen		Hungary	4032
88	Bacs-Kiskun Megyei Korhaz	Kecskemet		Hungary	6000
89	All India Institute of Medical Sciences	New Delhi	Delhi	India	110029
90	Tata Memorial Hospital	Mumbai,	Maharashtra	India	400012
91	Kokilaben Dhirubhai Ambani Hospital & Medical Research Insti	Mumbai	Maharashtra	India	400053
92	HCG Manavata Cancer Centre	Nashik	Maharashtra	India	422002
93	Jawaharlal Institute Of Postgraduate Medical Education and R	Gorimedu	Pondicherry	India	605006
94	Chittaranjan National Cancer Institute	Kolkata	West Bengal	India	700026
95	St Vincents University Hospital	Dublin		Ireland	DUBLIN 4
96	A.O.R.N. San Giuseppe Moscati	Avellino	Campania	Italy	83100
97	A.O.U. di Bologna Policlinico S.Orsola Malpighi	Bologna	Emilia-Romagna	Italy	40138
98	A.S.U. Friuli Centrale - A. Regionale Coordinamento Salute	Udine	Friuli-Venezia Giulia	Italy	33100
99	IRCCS Istituti Fisioterapici Ospitalieri - IFO	Roma	Lazio	Italy	00144
100	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma	Lazio	Italy	00168
101	IRCCS Ospedale Policlinico San Martino	Genova	Liguria	Italy	16132
102	Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.	Milano	Lombardia	Italy	20089
103	IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)	Milano	Lombardia	Italy	20141
104	ASST Grande Ospedale Metropolitano Niguarda	Milano	Lombardia	Italy	20162
105	Istituto Oncologico Veneto IRCCS (IOV)	Padova	Veneto	Italy	35128
106	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
107	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
108	Hokkaido University Hospital	Sapporo	Hokkaido	Japan	060-8648
109	The Cancer Institute Hospital of JFCR	Koto-ku	Tokyo	Japan	135-8550
110	Seoul National University Hospital	Seoul		Korea, Republic of	03080
111	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
112	Asan Medical Center	Seoul		Korea, Republic of	05505
113	Samsung Medical Center	Seoul		Korea, Republic of	06351
114	Korea University Anam Hospital	Seoul		Korea, Republic of	136-705
115	Radium Hospital Department of Oncology	Oslo		Norway	0379
116	Wojskowy Instytut Medyczny	Warszawa		Poland	04-141
117	Fundacao Champalimaud	Lisboa		Portugal	1400-038
118	CHULN - Hospital Santa Maria	Lisboa		Portugal	1649-035
119	Centro Hospitalar Universitario do Porto	Porto		Portugal	4099-001
120	IPO Porto	Porto		Portugal	4200-072
121	Arkhangelsk Clinical Oncology Dispensary	Arkhangelsk		Russian Federation	163045
122	Ltd "EVIMED"	Chelyabinsk		Russian Federation	454048
123	Republican Clinical Oncology Dispensary Kazan	Kazan		Russian Federation	420029
124	Moscow Clinical Scientific Centre n.a.Loginov	Moscow		Russian Federation	111123
125	Russian Oncological Scientific Center n.a. N.N. Blokhin RAMS	Moscow		Russian Federation	115478
126	1st Moscow State Medical University n.a. I.M.Sechenov	Moscow		Russian Federation	119435
127	Moscow Scient. Res. Institute of Oncology n.a P.A. Hertzen	Moscow		Russian Federation	125284
128	City Oncological Hospital #62	Moscow		Russian Federation	143423
129	Clinical Diagnostical Center	Nizhny Novgorod		Russian Federation	603006
130	St. Petersburg Clinical Onc. Cent. of Spec. Types of Care	St. Petersburg		Russian Federation	197758
131	National Cancer Center Singapore	Singapore		Singapore	169610
132	Onkologicky Ustav Svatej Alzbety, s.r.o.	Bratislava		Slovakia	812 50
133	Narodny onkologicky ustav	Bratislava		Slovakia	833 10
134	Institut Català d'Oncologia Hospitalet	Hospitalet de Llobregat	Barcelona	Spain	08907
135	Hospital Universitario "Marqués de Valdecilla"	Santander	Cantabria	Spain	39008
136	Hospital del Mar	Barcelona		Spain	08003
137	Ciutat Sanitària i Universitaria de la Vall d'Hebron	Barcelona		Spain	08035
138	Hospital Clínic i Provincial de Barcelona	Barcelona		Spain	08036
139	Hospital General Universitario Gregorio Marañón \| Oncología	Madrid		Spain	28007
140	Fundacion Jimenez Diaz (Clinica de la Concepcion)	Madrid		Spain	28040
141	Centro Integral Oncológico Clara Campal	Madrid		Spain	28050
142	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
143	Hospital General Universitario de Valencia	Valencia		Spain	46014
144	Karolinska Universitetssjukhuset i Solna	Stockholm		Sweden	171 76
145	Chang Gung Memorial Hospital Kaohsiung	Kaohsiung		Taiwan	833
146	National Taiwan University Hospital	Taipei		Taiwan	100
147	Tri-Service General Hospital	Taipei		Taiwan
148	Ankara Sehir Hastanesi	Ankara		Turkey	06800
149	Trakya Univ. Tip Fak.	Edirne		Turkey	22030
150	Istanbul Universitesi Istanbul Tip Fakultesi	Istanbul		Turkey	34093
151	Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi	Istanbul		Turkey	34098
152	TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has	Istanbul		Turkey	34724
153	Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma	Izmir		Turkey	35360
154	Erciyes Universitesi Tip Fakultesi	Kayseri		Turkey	38039
155	National Cancer Institute-Ukraine	Kiev		Ukraine	03022
156	Southampton General Hospital	Southampton	Hampshire	United Kingdom	SO16 6YD
157	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
158	Institute Of Cancer-Barts and The London School of Medicine	London		United Kingdom	EC1M 6BQ
159	University College Hospital	London		United Kingdom	W1T 7HA