A Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Participants Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04172675

Collaborator

(none)

280

Enrollment

179

Locations

Arms

89.4

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate recurrence-free survival (RFS) in participants treated with erdafitinib vs Investigator's Choice, for participants with high-risk non-muscle-invasive bladder cancer (NMIBC) who harbor fibroblast growth factor receptor (FGFR) mutations or fusions, and who recurred after bacillus calmette-guerin (BCG) therapy.

Condition or Disease	Intervention/Treatment	Phase
Urinary Bladder Neoplasms	Drug: Erdafitinib Drug: Investigator Choice (Gemcitabine) Drug: Investigator Choice (Mitomycin C)	Phase 2

Detailed Description

This study enrolls participants with high risk NMIBC and FGFR mutations or fusions. Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) 1-4 inhibitor with demonstrated clinical activity in participants with solid tumors, including urothelial carcinoma, with alterations in the FGFR pathway. In Cohort 1, participants will be randomized to erdafitinib or to Investigators Choice (intravesical gemcitabine or intravesical MMC/hyperthermic MMC). The study consists of Screening period, Treatment Phase and Follow-up Phase.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

280 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase 2 Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Subjects Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) and FGFR Mutations or Fusions

Actual Study Start Date :

Feb 28, 2020

Anticipated Primary Completion Date :

Oct 26, 2022

Anticipated Study Completion Date :

Aug 11, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1: Erdafitinib Participants with high-risk non-muscle-invasive bladder cancer (NMIBC) presenting as papillary tumor only (carcinoma in situ [CIS], absent), with disease recurrence after bacillus Calmette- Guerin (BCG) therapy will receive treatment with erdafitinib.	Drug: Erdafitinib Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days. Other Names: JNJ-42756493
Active Comparator: Cohort 1: Investigators Choice Participants with high-risk NMIBC presenting as papillary tumor only (CIS, absent), with disease recurrence after BCG therapy will receive the investigator's choice of either intravesical gemcitabine or intravesical mitomycin C (MMC)/hyperthermic MMC. Participants who are randomized to gemcitabine or MMC/hyperthermic MMC in Cohort 1 and demonstrate a recurrence via investigator disease assessment will have the opportunity to cross over to treatment with erdafitinib.	Drug: Investigator Choice (Gemcitabine) Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months. Drug: Investigator Choice (Mitomycin C) Investigator's Choice treatment will be given once weekly for at least 4 doses of induction followed by monthly maintenance for at least 6 months.
Experimental: Cohort 2 Participants with high-risk, BCG- unresponsive NMIBC presenting as CIS with or without concurrent papillary tumor will receive treatment with erdafitinib.	Drug: Erdafitinib Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days. Other Names: JNJ-42756493
Experimental: Cohort 3 Marker lesion study in intermediate-risk NMIBC presenting as papillary disease only. All enrolled participants will receive treatment with erdafitinib.	Drug: Erdafitinib Participants will receive erdafitinib orally beginning on Cycle 1 Day 1 until 2 years of treatment have been completed, disease recurrence, intolerable toxicity, withdrawal of consent, a decision by the investigator to discontinue treatment, or study termination, whichever occurs first. Each cycle is of 28 days. Other Names: JNJ-42756493

Outcome Measures

Primary Outcome Measures

Recurrence-Free Survival (RFS) [Up to 4 years]
RFS is defined as the time from the date of randomization until the date of the reappearance of high-risk disease, or death, whichever is reported first.

Secondary Outcome Measures

Time to Disease Worsening [Up to 4 years]
Time from the date of randomization to the date of first documented evidence of cystectomy, change in therapy indicative of more advanced disease (including systemic chemotherapy or radiotherapy). Participants who are free of disease worsening and alive or have unknown status will be censored at the last tumor assessment.
Time to Progression [Up to 4 years]
Time from the date of randomization until the date of first documented evidence of any of progression or death. Participants who are progression -free and alive or have unknown status will be censored at the date of the last tumor assessment.
Disease-Specific Survival [Up to 4 years]
The time from the date of randomization to the date of the participant's death resulting from bladder cancer. Participants who are alive or have unknown vital status will be censored at the date the participant was last known to be alive. Participants whose death result from causes other than bladder cancer will be censored at their death dates.
Overall Survival [Up to 4 years]
The time from the date of randomization to the date of the participant's death resulting from any cause. Participants who are alive or have unknown vital status will be censored at the date the participant was last known to be alive.
Recurrence-Free Survival [Months 6, 12, and 24]
RFS is defined as the time from the date of randomization until the date of the reappearance of high-risk disease, or death, whichever is reported first. Participants who are recurrence-free and alive or have unknown status will be censored at the last tumor assessment.
Recurrence-Free Survival 2 (RFS2) [Up to 4 years]
RFS2 is defined as the time from the date of randomization until the date of the reappearance of high-risk disease on the first subsequent non-surgical anticancer treatment, or death, whichever is reported first.
RFS by Central Histopathologic Review [Up to 4 years]
RFS will be assessed by central histopathologic review. RFS is defined as the time from the date of randomization until the date of the reappearance of high-risk disease, or death, whichever is reported first.
Plasma Concentration of Erdafitinib [Cycle 1 Day 14, Cycle 2 Day 1 (each cycle is of 28 days)]
Plasma concentration of erdafitinib will be reported.
Number of Participants with Adverse events [Up to 4 years]
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product
Change from Baseline in Patient's Global Impression of Severity (of cancer) (PGIS) [Baseline up to 4 years]
PGIS is single-item questionnaires to evaluate patient's global impression of severity.
Change from Baseline in Patient's Global Impression of Change (of cancer) (PGIC) [Baseline, Cycle 2 Day 1 and end of treatment (up to 2 years) (each cycle is of 28 days)]
PGIC is single-item questionnaires to evaluate a patient's global impression of change of cancer.
Change from Baseline in European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire (EORTC QLQ) -C30 [Baseline up to 4 years]
EORTC QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies.
Change from Baseline in EORTC QLQ- Non-Muscle-Invasive Bladder Cancer (NMIBC) 24 [Baseline up to 4 years]
EORTC QLQ-NMIBC24 is a 24-item questionnaire for evaluating the HRQoL of participants with superficial (non-muscle-invasive) bladder cancer. The questionnaire is designed to supplement the QLQ-C30.
Change from Baseline in EuroQol European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) [Baseline up to 4 years]
EQ-5D-5L is a standardized measure of health status developed by the EuroQol Group to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder. Variant pathology are allowed
Tumor with specified fibroblast growth factor receptor (FGFR) mutations or fusions
Bacillus Calmette- Guerin (BCG)-unresponsive after adequate BCG therapy or BCG experienced participants
Refuses or is not eligible for cystectomy (Cohort 1 and Cohort 2 only)
Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-1
Must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
A woman of childbearing potential must have a negative pregnancy test (beta-hCG [beta-human chorionic gonadotropin]) (urine or serum) within 7 days before randomization (Cohort 1) or the first dose of study drug (Cohort 2 and Cohort 3)
Adequate bone marrow, liver, and renal function as specified in the protocol

Exclusion Criteria:

Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder
Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder
Prior treatment with an FGFR inhibitor
Active malignancies other than the disease being treated under study. The only allowed exceptions are: (a) skin cancer treated within the last 24 months that is considered completely cured (b) adequately treated lobular carcinoma in situ (LCIS) and ductal CIS (c) history of localized breast cancer and receiving antihormonal agents, or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy
Current central serous retinopathy or retinal pigment epithelial detachment of any grade

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urological Associates of Southern Arizona, P.C.	Tucson	Arizona	United States	85741
2	USC Institute of Urology	Los Angeles	California	United States	90033
3	The Urology Center of Colorado	Denver	Colorado	United States	80211
4	Foothills Urology - Golden Off	Golden	Colorado	United States	80401-5027
5	Urological Research Network	Hialeah	Florida	United States	33016
6	Tampa General Hospital	Tampa	Florida	United States	33578
7	Emory University - Winship Cancer Institute	Atlanta	Georgia	United States	30322
8	Northwestern University	Chicago	Illinois	United States	60611
9	Simmons Cancer Institute	Springfield	Illinois	United States	62702
10	University of Kansas	Westwood	Kansas	United States	66205
11	University of Kentucky	Lexington	Kentucky	United States	40536
12	LCMC Health	Metairie	Louisiana	United States	70006
13	Ochsner LSU Health Shreveport - Regional Urology	Shreveport	Louisiana	United States	71106
14	MI Medicine	Ann Arbor	Michigan	United States	48109
15	University of Missouri	Columbia	Missouri	United States	65212
16	Albany Medical College	Albany	New York	United States	12208
17	Montefiore Medical Center	Bronx	New York	United States	10461
18	NYU Langone Health	New York	New York	United States	10016
19	Strong Memorial Hospital University of Rochester	Rochester	New York	United States	16442
20	Great Lakes Physician PC d/b/a Western New York Urology Associates	Sanborn	New York	United States	14132
21	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
22	The Urology Group	Cincinnati	Ohio	United States	45212
23	The Ohio State University- James Cancer Hospital	Columbus	Ohio	United States	43210
24	Oregon Health & Science University	Portland	Oregon	United States	97239
25	MidLantic Urology	Bala-Cynwyd	Pennsylvania	United States	19004
26	Lancaster Urology	Lancaster	Pennsylvania	United States	17604
27	University of Pittsburgh Medical Center - Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
28	Urology Associates	Nashville	Tennessee	United States	37209
29	UT Southwestern Medical Center	Dallas	Texas	United States	75390-8565
30	University of Washington	Seattle	Washington	United States	98008
31	William S. Middleton Memorial VA	Madison	Wisconsin	United States	53705
32	Medical College of Wisconsin-Froedtert Hospital	Milwaukee	Wisconsin	United States	53226
33	Hospital Sirio Libanes	Buenos Aires		Argentina	C1419AHN
34	Hospital Britanico de Buenos Aires	Buenos Aires		Argentina
35	CEMIC Saavedra	Ciudad Autonoma de Buenos Aires		Argentina	C1431FWN
36	Hospital Italiano de Buenos Aires	Ciudad Autonoma de		Argentina	C1199ABB
37	Cemaic - Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica	Cordoba		Argentina	5000
38	Centro Urologico Profesor Bengio	Cordoba		Argentina	X5000KPH
39	Hospital Privado de Cordoba	Cordoba		Argentina	XX5016KEH
40	Flinders Medical Centre	Bedford Park		Australia	5042
41	St. Vincent's Hospital Sydney	Darlinghurst		Australia	2010
42	Macquarie University	Macquarie University		Australia	2109
43	Peter MacCallum Cancer Centre	Melbourne		Australia	3000
44	Newcastle Private Hospital	New Lambton Heights		Australia	2305
45	ICON Cancer Care	South Brisbane		Australia	4101
46	Sydney Adventist Hospital	Wahroonga		Australia	2076
47	Princess Alexandra Hospital	Woolloongabba		Australia	4102
48	Cliniques Universitaires Saint Luc	Brussel		Belgium	1200
49	AZ Maria Middelares	Gent		Belgium	9000
50	UZ Leuven	Leuven		Belgium	3000
51	CHU Sart-Tilman	Liege		Belgium	4000
52	Algemeen Ziekenhuis Delta	Roeselare		Belgium	8800
53	Hospital Erasto Gaertner	Curitiba		Brazil	81520-060
54	Oncocentro Ceará	Fortaleza		Brazil	60135-237
55	Hospital Araújo Jorge da Associação de Combate ao Câncer em Goiás	Goiânia		Brazil	74605-070
56	Liga Norte Riograndense Contra O Cancer	Natal		Brazil	59075-740
57	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre		Brazil	90050170
58	Hospital Nossa Senhora da Conceicao	Porto Alegre		Brazil	91410-330
59	Instituto de Medicina Integral Professor Fernando Figueira	Recife		Brazil	50070-550
60	Hospital das Clinicas da Faculdade de Medicina da USP de Ribeirao Preto	Ribeirão Preto		Brazil	14048 900
61	Oncoclínicas	Rio de Janeiro		Brazil	22250-905
62	Instituto COI de Pesquisa, Educacao e Gestao	Rio de Janeiro		Brazil	22793-080
63	Faculdade de Medicina Do Abc	Santo André		Brazil	09060-650
64	Instituto do Cancer do Estado de Sao Paulo ICESP	Sao Paulo		Brazil	01246-000
65	Hospital Do Servidor Publico Estadual	Sao Paulo		Brazil	04039-004
66	Hospital Sirio Libanes	São Paulo		Brazil	01308-050
67	Nanjing Drum Tower Hospital	Nanjing		China	210008
68	Fudan University Shanghai Cancer Center	Shanghai		China	200032
69	Renji Hospital, Shanghai Jiaotong University School of Medicine	Shanghai		China	200240
70	Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology	Wuhan		China	430030
71	Fakultni nemocnice u sv. Anny v Brne	Brno		Czechia	656 91
72	Krajská nemocnice Liberec	Liberec		Czechia	460 63
73	Urologicka klinika FNOL	Olomouc		Czechia	775 20
74	Vseobecna fakultni nemocnice v Praze	Praha 2		Czechia	128 08
75	Fakultni nemocnice v Motole	Praha 5		Czechia	150 06
76	Hôpital Pellegrin CHU Bordeaux	Bordeaux		France	33076
77	CHU Gabriel-Montpied	Clermont Ferrand		France	63000
78	Hopital Huriez	Lille		France	59037
79	Hôpital Edouard Herriot	Lyon Cedex 03		France	69437
80	Institut Paoli Calmettes	Marseille Cedex 9		France	13273
81	Hôpital Universitaire Pitié-Salpêtrière	Paris		France	75013
82	Groupe Hospitalier Diaconesses Croix Saint Simon	Paris		France	75020
83	Hopital Bichat Claude Bernard	Paris		France	75877
84	CHU De Poitiers	Poitiers		France	86021
85	Chu Rennes - Hopital Pontchaillou	Rennes Cedex		France	35033
86	Hopital Charles Nicolle	Rouen		France	76031
87	CHP Saint Gregoire	Saint Gregoire		France	35760
88	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse		France	31000
89	Centre Hospitalier Universitaire de Nancy - Hôpital Central	Vandœuvre-lès-Nancy Cedex		France	54519
90	Gustave Roussy	Villejuif Cedex		France	94800
91	GFO Kliniken Rhein Berg	Bergisch-Gladbach		Germany	51465
92	Urologicum Duisburg	Duisburg		Germany	47169
93	Praxis Dr. med. Stefan Carl	Emmendingen		Germany	79312
94	Klinikum Herne - Urologie	Herne		Germany	44625
95	Universitätsklinikum Schleswig Holstein Campus Lübeck	Lubeck		Germany	23538
96	Klinikum rechts der Isar - III. Med. Klinik und Poliklinik	Muenchen		Germany	81675
97	Universitaetsklinikum Muenster	Muenster		Germany	48149
98	Praxisklinik Urologie Rhein/Ruhr - Germany	Mülheim an der Ruhr		Germany	45468
99	MVZ Urologie 24 gGmbH	Nuernberg		Germany	90491
100	Studienpraxis Urologie Drs. Feyerabend	Nuertingen		Germany	72622
101	CUROS - Uberörtliche urologische Gemeinschaftspraxis	Wesseling		Germany	50389
102	Health Care Global Enterprises pvt Ltd	Bangalore		India	560027
103	S.P.Medical College & AG of Hospitals	Bikaner		India	334003
104	Rajiv Gandhi Cancer Institute & Research Centre	Delhi		India	110085
105	Health Care Global Enterprises	Jaipur		India	302020
106	Tata Medical Center	Kolkata		India	700160
107	King George's Medical University	Lucknow		India	226003
108	Meenakshi Mission Hospital and Research Center	Madhurai		India	625107
109	Tata Memorial Hospital	Mumbai		India	400012
110	Muljibhai Patel Urological Hospital	Nadiad		India	387001
111	CIMET's Inamdar Multispeciality Hospital	Pune		India	411040
112	Generale Regionale F. Miulli	Acquaviva delle Fonti		Italy	70021
113	Ospedale Regionale Umberto Parini	Aosta		Italy	11100
114	Fondazione Istituto G. Giglio	Cefalu		Italy	90015
115	Ospedale Civile di Guastalla	Guastalla		Italy	42016
116	Azienda Ospedaliera ''Vito Fazzi''	Lecce		Italy	73100
117	UOC Oncologia Ospedale Provinciale di Macerata	Macerata		Italy	62100
118	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
119	IRCCS Ospedale San Raffaele	Milan		Italy	20132
120	Humanitas Centro Catanese di Oncologia	Misterbianco/Catania		Italy	95045
121	Fondazione G. Pascale - Istituto Nazionale Tumori IRCCS	Napoli		Italy	80138
122	Azienda Ospedaliera Sant Andrea	Roma		Italy	00189
123	Azienda Ospedaliera Universitaria Integrata Verona	Verona		Italy	37126
124	Juntendo University Hospital	Bunkyo-Ku		Japan	113-8431
125	Tokyo Medical and Dental University Hospital	Bunkyo-Ku		Japan	113-8519
126	Asahi General Hospital	Chiba		Japan	289-2511
127	Hakodate Goryokaku Hospital	Hakodate		Japan	040-8611
128	Saitama Medical University International Medical Center	Hidaka		Japan	350-1298
129	Hitachi General Hospital	Hitachi		Japan	317-0077
130	St.Marianna University Hospital	Kanagawa		Japan	216-8511
131	Nagoya University Hospital	Nagoya		Japan	466-8560
132	JOHAS Osaka Rosai Hospital	Osaka		Japan	591-8025
133	Gunma Prefectural Cancer Center	Ota		Japan	373-8550
134	Osaka Medical and Pharmaceutical University Hospital	Takatsuki		Japan	569-8686
135	Toranomon Hospital	Tokyo		Japan	105-8470
136	The Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
137	Fujita Health University Hospital	Toyoake		Japan	470-1192
138	University of Tsukuba Hospital	Tsukuba-City		Japan	305-8576
139	Yokohama City University Medical Center	Yokohama		Japan	232-0024
140	Pusan National University Hospital	Busan		Korea, Republic of	49241
141	Chungbuk National University Hospital	Cheongju		Korea, Republic of	361-711
142	Kyungpook National University Chilgok Hospital	Daegu		Korea, Republic of	41404
143	National Cancer Center	Goyang-si		Korea, Republic of	10408
144	Chonnam National University Hwasun Hospital	Jeollanam-do		Korea, Republic of	58128
145	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
146	Seoul National University Hospital	Seoul		Korea, Republic of	03080
147	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
148	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
149	Samsung Medical Center	Seoul		Korea, Republic of	06351
150	Uniwersyteckie Centrum Kliniczne	Gdańsk		Poland	80-214
151	Pratia MCM Krakow	Krakow		Poland	30-510
152	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lodz		Poland	93-513
153	CRC Sp. z o.o.	Poznan		Poland	60-848
154	Kliniczny Szpital Wojewodzki nr 1 w Rzeszowie	Rzeszow		Poland	35-055
155	Samodzielny Publiczny Szpital Kliniczny nr 2 PUM	Szczecin		Poland	70-111
156	City Clinic Sp. z o.o.	Warszawa		Poland	02-473
157	Medical Concierge Centrum Medyczne	Warszawa		Poland	02-798
158	Uniwersytecki Szpital Kliniczny	Wroclaw		Poland	50-556
159	Dolnoslaskie Centrum Onkologii	Wroclaw		Poland	53-413
160	Fundacion Puigvert	Barcelona		Spain	08025
161	Hosp. Clinic I Provincial de Barcelona	Barcelona		Spain	8036
162	Hosp. Univ. Ramon Y Cajal	Madrid		Spain	28034
163	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
164	Hosp. Univ. La Paz	Madrid		Spain	28046
165	Corporacio Sanitari Parc Tauli	Sabadell		Spain	08208
166	Hosp. Univ. Marques de Valdecilla	Santander		Spain	39008
167	Instituto Valenciano de Oncologia	Valencia		Spain	46009
168	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	80756
169	China Medical University Hospital	Taichung		Taiwan	40447
170	Taichung Veterans General Hospital	Taichung		Taiwan	40705
171	National Taiwan University Hospital	Taipei		Taiwan	10002
172	Taipei Veterans General Hospital	Taipei		Taiwan	11217
173	Chang Gung Memorial Hospital- Linkou	Taoyuan County		Taiwan	33305
174	Royal Surrey County Hospital NHS Trust	Guildford		United Kingdom	GU2 7XX
175	University College London Hospitals	London		United Kingdom	NW1 2BU
176	The Christie NHS Foundation Trust - Christie Hospital	Manchester		United Kingdom	M20 4BX
177	South Tees Hospital NHS Foundation Trust-The James Cook University Hospital	Middlesborough		United Kingdom	TS4 3BW
178	Universirty of Sheffield Teaching Hospitals NHS Trust	Sheffield		United Kingdom	S10 2JF
179	Lister Hospital	Stevenage		United Kingdom	SG1 4AB