Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer

Sponsor

NuCana plc (Other)

Overall Status

Terminated

CT.gov ID

NCT04163900

Collaborator

(none)

775

Enrollment

125

Locations

Arms

26.3

Actual Duration (Months)

6.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

NuTide:121 compares NUC-1031 with gemcitabine, both in combination with cisplatin, in patients with previously untreated advanced biliary tract cancer.

The primary hypotheses are:

The combination of NUC-1031 plus cisplatin prolongs overall survival compared to the gemcitabine plus cisplatin standard of care
The combination of NUC-1031 plus cisplatin increases overall response rate compared to the gemcitabine plus cisplatin standard of care

Condition or Disease	Intervention/Treatment	Phase
Biliary Tract Cancer	Drug: NUC-1031 Drug: Gemcitabine Drug: Cisplatin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

775 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

1:1 randomization model to either Arm A or Arm B1:1 randomization model to either Arm A or Arm B

Masking:

Single (Outcomes Assessor)

Masking Description:

Imaging scans will be assessed by blinded independent review according to RECIST v1.1

Primary Purpose:

Treatment

Official Title:

A Phase III Open-Label, Multi-Centre, Randomized Study Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Previously Untreated Locally Advanced or Metastatic Biliary Tract Cancer

Actual Study Start Date :

Dec 24, 2019

Actual Primary Completion Date :

Mar 2, 2022

Actual Study Completion Date :

Mar 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A - NUC-1031 and cisplatin 725 mg/m^2 NUC-1031 administered in combination with 25 mg/m^2 cisplatin on Days 1 and 8 of a 21-day cycle	Drug: NUC-1031 IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes Other Names: fosgemcitabine palabenamide Drug: Cisplatin IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol Other Names: CDDP
Active Comparator: B - gemcitabine and cisplatin 1000 mg/m^2 gemcitabine administered in combination with 25 mg/m^2 cisplatin on Days 1 and 8 of a 21-day cycle	Drug: Gemcitabine IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert Other Names: Difluorodeoxycytidine Gemzar Drug: Cisplatin IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol Other Names: CDDP

Arm

Intervention/Treatment

Experimental: A - NUC-1031 and cisplatin

725 mg/m^2 NUC-1031 administered in combination with 25 mg/m^2 cisplatin on Days 1 and 8 of a 21-day cycle

Drug: NUC-1031

IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes

Other Names:

fosgemcitabine palabenamide

Drug: Cisplatin

IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

Other Names:

CDDP

Active Comparator: B - gemcitabine and cisplatin

1000 mg/m^2 gemcitabine administered in combination with 25 mg/m^2 cisplatin on Days 1 and 8 of a 21-day cycle

Drug: Gemcitabine

IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert

Other Names:

Difluorodeoxycytidine

Gemzar

Drug: Cisplatin

IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

Other Names:

CDDP

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [Evaluated on an ongoing basis from randomization, then every 12 weeks from the date of treatment discontinuation until the date of death from any cause, up to a maximum of 18 months after the last patient starts treatment]
The median time, in months, from the date of randomization to the date of death from any cause
Objective response rate (ORR) [Evaluated every 9 weeks from start of treatment or, where treatment is stopped with no evidence of progression, every 12 weeks until disease progression or death from any cause, up to a maximum of 18 months after the last patient starts treatment.]
Percentage of patients achieving a confirmed complete or partial response to treatment as assessed by blinded independent review according to RECIST v1.1 criteria in patients with measurable disease at baseline. Patients will receive a confirmatory scan 28-42 days after response is first observed

Secondary Outcome Measures

Progression-free survival (PFS) [Evaluated every 9 weeks from start of treatment or, where treatment is stopped with no evidence of progression, every 12 weeks until disease progression or death from any cause, up to a maximum of 18 months after the last patient starts treatment]
Based on blinded independent review according to RECIST v1.1 criteria and defined as the time from randomization to the first observation of objective tumour progression or death from any cause
Duration of response (DoR) [Evaluated every 9 weeks from initial clinical response or, where treatment is stopped with no evidence of progression, every 12 weeks until disease progression or death from any cause, up to a maximum of 18 months after the last patient starts treatment]
Defined as the time from initial clinical response to the first observation of tumour progression or death from any cause as assessed by blinded independent review
12-month survival [12 months from randomization]
Proportion of patients still alive at 12 months from randomization
18-month survival [18 months from randomization]
Proportion of patients still alive at 18 months from randomization
Disease control rate (DCR) [Evaluated every 9 weeks from start of treatment or, where treatment is stopped with no evidence of progression, every 12 weeks until disease progression or death from any cause, up to a maximum of 18 months after the last patient starts treatment]
Based on blinded independent review according to RECIST v1.1, defined as the percentage of patients demonstrating a Best Overall Response of Complete Response, Partial Response or Stable Disease
Safety and tolerability [Adverse events that occur from initiation of therapy until 30 day post-treatment will be recorded. Adverse events that are not resolved at this time will be followed until resolution to baseline value.]
Safety and tolerability will be assessed by total incidence of Treatment Emergent Adverse Events (TEAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Maximum observed plasma concentration (Cmax) of NUC-1031, dFdC and dFdU will be compared to existing data using simulations in Arm A only [Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)]
Area under the plasma concentration-time curve (AUC) of NUC-1031, dFdC and dFdU will be compared to existing data using simulations in Arm A only [Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)]
Elimination half-life (t½) of NUC-1031, dFdC and dFdU using descriptive statistics in Arm A only [Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)]
Terminal elimination rate constant (λz) of NUC-1031, dFdC and dFdU using descriptive statistics in Arm A only [Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)]
Clearance of NUC-1031, dFdC and dFdU will be compared to existing data using simulations in Arm A only [Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)]
Volume of distribution of NUC-1031, dFdC and dFdU will be compared to existing data using simulations in Arm A only [Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)]
Comparison of patient-reported quality of life (QoL) scores in Arm A and Arm B [Assessed at screening, on Day 1 of every cycle (each cycle is 21 days), and 30 days post-treatment]
Assessed using the European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ-C30) using the QLQ-BIL21 module
Comparison of patient-reported quality of life (QoL) scores in Arm A and Arm B [Assessed at screening, on Day 1 of every cycle (each cycle is 21 days), and 30 days post-treatment]
Assessed using the 5-level EuroQol five-dimension scale (EQ-5D-5L)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Written informed consent and authorization to use and disclose health information.
Ability to comprehend and willingness to comply with the requirements of this protocol, including the QoL questionnaires.
Female or male patients aged ≥18 years.
Histologically- or cytologically-confirmed adenocarcinoma of the biliary tract (including gallbladder, intra and extra-hepatic biliary ducts and ampullary cancers) that is locally advanced, unresectable or metastatic (AJCC edition 8, 2018). Patients with measurable (as per RECIST v1.1 criteria) or non-measurable disease are permitted.
Life expectancy ≥16 weeks.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Adequate biliary drainage with no evidence of ongoing infection. If applicable, treatable and clinically-relevant biliary duct obstruction has been relieved by internal endoscopic drainage/stenting at least 2 weeks previously or by palliative bypass surgery or percutaneous drainage prior to study treatment, and the patient has no active or suspected uncontrolled infection. Patients fitted with a biliary stent should be clinically stable and free of signs of infection for ≥2 weeks prior to study treatment. Patients with improving biliary function who meet all other inclusion criteria may be re-tested during the screening window.
Adequate bone marrow, hepatic, and renal function, as evidenced by:

Absolute neutrophil count (ANC) ≥1,500/μL without colony-stimulating factor support
Platelet count ≥100,000/μL
Haemoglobin ≥9 g/dL without need for haematopoietic growth factor or transfusion support in prior 2 weeks
Total bilirubin <2 × upper limit of normal (ULN); does not apply to patients with Gilbert's syndrome. Consistent with inclusion criterion 7, patients whose whole bilirubin and biliary function is recovering may be re-tested during the screening period.
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) <5 × ULN
Creatinine clearance ≥45 mL/min actual or calculated by the Cockcroft-Gault method
International normalized ratio (INR) <1.5 and activated partial thromboplastin time (aPTT) <1.5 × ULN; does not apply to patients on an anti-coagulant with stable dose 28 days prior to first dose.

QTc interval <450 msec (males) or <470 msec (females), in the absence of bundle branch block. In the presence of bundle branch block with consequent QTc prolongation, patients may be enrolled based on a careful risk-benefit assessment.
Human Immunodeficiency Virus-infected patients who are healthy and have a low risk of Acquired Immunodeficiency Syndrome-related outcomes may be included in this study.
Female patients of child-bearing potential (i.e., all women except those who are post-menopausal for ≥1 year or who have a history of hysterectomy or surgical sterilization) must have a negative pregnancy test within 3 days prior to the first study drug administration. All patients of child-bearing potential must agree to practice true abstinence or to use two highly effective forms of contraception, one of which must be a barrier method of contraception, from the time of screening until 6 months after the last dose of study medication.
Male patients with a female partner must either have had a successful vasectomy or they and their female partner meet the criteria above (not of childbearing potential or practicing highly effective contraceptive methods).

Exclusion Criteria:

Combined or mixed hepatocellular/cholangiocarcinoma.
Prior systemic therapy for advanced or metastatic biliary tract cancer. However, prior chemotherapy in the adjuvant setting or low-dose chemotherapy given in conjunction with radiotherapy in the adjuvant setting and completed at least 6 months prior to enrolment is permitted. The following prior interventions are allowed provided the patient has fully recovered:

Surgery: non-curative resection with macroscopic residual disease or palliative bypass surgery. Patients who have previously undergone curative surgery must now have evidence of non-resectable disease requiring systemic chemotherapy.
Radiotherapy: prior radiotherapy (with or without radio-sensitizing low-dose chemotherapy) for localized disease and there is now clear evidence of disease progression requiring systemic chemotherapy.
Photodynamic therapy: prior photodynamic therapy for localized disease with no evidence of metastatic disease or for localized disease to relieve biliary obstruction in the presence of metastatic disease provided there is now clear evidence of disease progression requiring systemic chemotherapy.
Palliative radiotherapy: palliative radiotherapy provided that all adverse events have resolved and the patient has measurable disease outside the field of radiation.

Prior treatment with or known hypersensitivity to NUC-1031, gemcitabine, cisplatin or other platinum-based agents or history of allergic reactions attributed to any parenteral excipients (e.g. dimethylacetamide [DMA], Cremophor EL, Polysorbate 80, Solutol HS 15).
Symptomatic central nervous system or leptomeningeal metastases.
History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, surgically excised or potentially curatively treated ductal carcinoma in situ of the breast, or low grade prostate cancer or patients after prostatectomy not requiring treatment. Patients with previous invasive cancers are eligible if treatment was completed more than 3 years prior to initiating the current study treatment, and the patient has had no evidence of recurrence since then.
Concurrent serious (as deemed by the Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, or other co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation.
Congenital or acquired immunodeficiency (e.g., serious active infection with HIV). As per inclusion criterion 10, patients with HIV who are healthy and have a low risk of AIDS related outcomes are eligible.
Other acute or chronic medical, neurological, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
Prior exposure to another investigational agent within 28 days prior to randomization.
Major surgery within 28 days prior to randomization; patient must have completely recovered from any prior surgical or other procedures.
Pregnant or breastfeeding.
Residual toxicities from prior treatments or procedures which have not regressed to Grade ≤1 severity (CTCAE v5.0), except for alopecia or ≤ Grade 2 peripheral neuropathy.
Concomitant use of drugs at doses known to cause clinically relevant prolongation of QT/QTc interval.
Administration of a live vaccination within 28 days prior to randomization.
Ongoing or recent (≤6 months) hepatorenal syndrome.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates , PC - HOPE	Tucson	Arizona	United States	85711
2	University of Arizona Cancer Center	Tucson	Arizona	United States	85719
3	The Oncology Institute of Hope and Innovation	Whittier	California	United States	90602-3171
4	Rocky Mountain Cancer Centers, LLP- Aurora	Aurora	Colorado	United States	80012
5	Baptist Health Medical Group Oncology, LLC	Miami	Florida	United States	33176
6	Orlando Health, Inc.	Orlando	Florida	United States	32806
7	IACT Health	Columbus	Georgia	United States	31904
8	Affiliated Oncologists LLC	Chicago Ridge	Illinois	United States	60415
9	University of Kansas Medical Center Research Institute, Inc.	Westwood	Kansas	United States	66205
10	Norton Cancer Institute	Louisville	Kentucky	United States	40217
11	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
12	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215-5400
13	Henry Ford Medical Group	Detroit	Michigan	United States	48202
14	Minnesota Oncology Hemtology	Minneapolis	Minnesota	United States	55404
15	Regents of the University of Minnesota	Minneapolis	Minnesota	United States	55455
16	University of Rochester Medical Center - Strong Memorial Hospital	Rochester	New York	United States	14642
17	The Research Foundation for The State University of New York	Stony Brook	New York	United States	11794-3369
18	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
19	The Ohio State University James Cancer Hospital and Solove Research Institute	Columbus	Ohio	United States	43210
20	Corporal Michael J. Crescenz VA Medical Center	Philadelphia	Pennsylvania	United States	19104
21	Prisma Health Upstate	Greenville	South Carolina	United States	29605
22	Texas Oncology, P.A. - Austin	Austin	Texas	United States	78705
23	Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
24	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410
25	Texas Oncology, P.A. - Tyler	Tyler	Texas	United States	75702
26	Virginia Mason Medical Center	Seattle	Washington	United States	98101
27	Northwest Cancer Specialists, P.C.-Vancouver	Vancouver	Washington	United States	98684
28	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
29	The Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin	United States	53226
30	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
31	St George Hospital	Kogarah	New South Wales	Australia	2217
32	Newcastle Private Hospital	Newcastle	New South Wales	Australia	2305
33	Westmead Hospital	Westmead	New South Wales	Australia	2145
34	Townsville Cancer Centre	Townsville	Queensland	Australia	4814
35	Warringal Medical Centre	Heidelberg	Victoria	Australia	3084
36	The Alfred Hospital	Melbourne	Victoria	Australia	3004
37	Fiona Stanley Hospital	Murdoch	Western Australia	Australia	6150
38	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
39	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
40	Nova Scotia Health Authority	Halifax	Nova Scotia	Canada	B3H1V7
41	Royal Victoria Regional Health Centre	Barrie	Ontario	Canada	L4M 6M2
42	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
43	Sunnybrook Research Institute	Toronto	Ontario	Canada	M4N 3M5
44	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 1X6
45	CHUM Centre de Recherche	Montréal	Quebec	Canada	H2X 0A9
46	SMBD Jewish General Hospital	Montréal	Quebec	Canada	H3T 1E2
47	Fakultní nemocnice Brno	Brno		Czechia	625 00
48	Fakultní nemocnice Hradec Králové	Hradec Králové		Czechia	500 05
49	Fakultní nemocnice Olomouc	Olomouc		Czechia	775 20
50	Thomayerova nemocnice	Prague		Czechia	140 59
51	Nemocnice Na Homolce	Prague		Czechia	150 30
52	Centre Georges François Leclerc	Dijon		France	21079
53	CHU de Grenoble - Hôpital Nord	Grenoble		France	38043
54	Institut Hospitalier Franco-Britannique	Levallois-Perret		France	92300
55	Hôpital Cochin	Paris		France	75679
56	ICO - Site René Gauducheau	Saint Herblain		France	44805
57	Universitaetsklinikum Heidelberg	Heidelberg	Baden Wuerttemberg	Germany	69120
58	Vivantes Klinikum Neukoelln	Berlin		Germany	12351
59	Universitaetsklinikum Freiburg	Freiburg		Germany	79106
60	Medizinische Hochschule Hannover	Hanover		Germany	30625
61	Universitaetsklinikum Tuebingen	Tuebingen		Germany	72076
62	Semmelweis Egyetem	Budapest		Hungary	1083
63	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest		Hungary	1097
64	Orszagos Onkologiai Intezet	Budapest		Hungary	1122
65	Debreceni Egyetem	Debrecen		Hungary	4032
66	Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz	Miskolc		Hungary	3526
67	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok		Hungary	5004
68	Ospedale Policlinico San Martino	Genova		Italy	16132
69	IEO Istituto Europeo di Oncologia	Milano		Italy	20141
70	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli		Italy	80131
71	IOV - Istituto Oncologico Veneto IRCCS	Padova		Italy	35128
72	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56126
73	Centro Ricerche Cliniche di Verona S.r.l	Verona		Italy	37124
74	CHA Bundang Medical Center, CHA University	Seongnam-si	Gyeonggi-do	Korea, Republic of	13496
75	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-do	Korea, Republic of	58128
76	Dong-A University Hospital	Pusan		Korea, Republic of	602-715
77	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13620
78	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
79	Seoul National University Hospital	Seoul		Korea, Republic of	03080
80	Samsung Medical Center	Seoul		Korea, Republic of	06351
81	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
82	Severance Hospital, Yonsei University	Seoul		Korea, Republic of	3722
83	Asan Medical Center	Seoul		Korea, Republic of	5505
84	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow		Russian Federation	115478
85	FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin	Moscow		Russian Federation	115478
86	"VitaMed" LLC	Moscow		Russian Federation	129515
87	State Budget Institution of Healthcare "Leningrad Regional Clinical Oncology Dispensary"	Saint Petersburg		Russian Federation	191104
88	Pavlov First Saint Petersburg State Medical University	Saint Petersburg		Russian Federation	197022
89	SPb SBIH "City Clinical Oncological Dispensary"	Saint Petersburg		Russian Federation	197022
90	Medicinskiy gorod	Tyumen		Russian Federation	625041
91	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
92	Hospital Clinic de Barcelona	Barcelona		Spain	08036
93	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
94	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet De Llobregat		Spain	08908
95	Hospital General Universitario Gregorio Marañon	Madrid		Spain	28007
96	Hospital Universitario Clinico San Carlos	Madrid		Spain	28040
97	Hospital Universitario HM Madrid Sanchinarro	Madrid		Spain	28050
98	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
99	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
100	Changhua Christian Medical Foundation Changhua Christian Hospital	Changhua		Taiwan	50004
101	China Medical University Hospital	Taichung		Taiwan	40447
102	National Taiwan University Hospital	Taipei		Taiwan	10016
103	MacKay Medical Foundation The Presbyterian Church in Taiwan MacKay Memorial Hospital	Taipei		Taiwan	10449
104	Taipei Veterans General Hospital	Taipei		Taiwan	11217
105	Acibadem Adana Hospital	Adana		Turkey	01130
106	Baskent University Adana Application and Research Center	Adana		Turkey	01220
107	Akdeniz University Medical Faculty	Antalya		Turkey	07058
108	Trakya University Medical Faculty	Edirne		Turkey	22030
109	Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
110	Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital	Malatya		Turkey	06105
111	Inonu University Medical Facility	Malatya		Turkey	44280
112	CI Chernivtsi RC Oncological Dispensary	Chernivtsi		Ukraine	58013
113	Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU	Kharkiv		Ukraine	61070
114	CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection	Kharkiv		Ukraine	61166
115	Kyiv City Clinical Oncological Center	Kyiv		Ukraine	03115
116	SI "Shalimov's National Institute of Surgery and Transplantation" of NAMSU	Kyiv		Ukraine	03126
117	Treatment-Prevention Institution Volyn Regional Oncological Dispensary	Luts'k		Ukraine	43018
118	Communal Institution Odesa Regional Clinical Hospital	Odesa		Ukraine	65025
119	RCI Sumy Regional Clinical Oncological Dispensary	Sumy		Ukraine	40022
120	Guy's Hospital	London	Greater London	United Kingdom	SE1 9RY
121	The Christie	Manchester	Greater Manchester	United Kingdom	M20 4BX
122	Western General Hospital	Edinburgh		United Kingdom	EH4 2XU
123	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 OYN
124	Torbay Hospital	Torquay		United Kingdom	TQ2 7AA
125	The Clatterbridge Cancer Centre	Wirral		United Kingdom	CH63 4JY