CUPISCO: A Phase II Randomized Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03498521

Collaborator

Foundation Medicine, Inc. (Other)

790

Enrollment

162

Locations

Arms

70.7

Anticipated Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will compare the efficacy and safety of molecularly-guided therapy versus standard platinum-containing chemotherapy in participants with poor-prognosis cancer of unknown primary site (CUP; non-specific subset) who have achieved disease control after 3 cycles of first-line platinum based induction chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Cancer of Unknown Primary Site	Drug: Alectinib Drug: Vismodegib Drug: Ipatasertib Drug: Olaparib Drug: Erlotinib Drug: Bevacizumab Drug: Vemurafenib Drug: Cobimetinib Drug: Trastuzumab Subcutaneous (SC) Drug: Pertuzumab Drug: Atezolizumab Drug: Carboplatin Drug: Paclitaxel Drug: Cisplatin Drug: Gemcitabine Drug: Entrectinib Drug: Ivosidenib Drug: Pemigatinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

790 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Randomized, Active-Controlled, Multi-Center Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Guided by Genomic Profiling Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site Who Have Received Three Cycles of Platinum Doublet Chemotherapy

Actual Study Start Date :

Jul 10, 2018

Anticipated Primary Completion Date :

Feb 28, 2023

Anticipated Study Completion Date :

May 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Molecularly-Guided Therapy Participants will be assigned to molecularly-guided therapy based on genomic profile.	Drug: Alectinib Alectinib will be administered orally at the label-recommended dose (600 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months). Drug: Vismodegib Vismodegib will be administered orally at the label-recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months). Drug: Ipatasertib Ipatasertib will be administered orally at the label-recommended dose (400 mg) once daily on Days 1-21 of each 28-day Cycle in combination with paclitaxel, and as monotherapy after the final administration of paclitaxel, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months). Drug: Olaparib Olaparib will be administered orally at the label-recommended dose (400 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months). Drug: Erlotinib Erlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months) Drug: Bevacizumab Bevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months) Drug: Vemurafenib Vemurafenib will be administered orally, 960 mg twice daily, in combination with Cobimetinib, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months) Drug: Cobimetinib Cobimetinib will be administered orally, 60mg once daily, in combination with Vemurafenib, on Days 1-21 of each 28-day Cycle, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months) Drug: Trastuzumab Subcutaneous (SC) Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months) Drug: Pertuzumab Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months) Drug: Atezolizumab Atezolizumab will be administered intravenously at the label-recommended dose (1200 mg), alone or in combination with chemotherapy, every 3 weeks until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months). Drug: Paclitaxel Paclitaxel will be administered intravenously, 175 mg/m^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC Drug: Entrectinib Entrectinib will be administered orally at the label-recommended dose (600 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months). Drug: Ivosidenib Ivosidenib will be administered orally at the label-recommended dose (500mg) once daily across a 28-day treatment cycle until loss of clinical benefit or unacceptable toxicity. Drug: Pemigatinib Pemigatinib will be administered orally at the label-recommended dose (13.5mg) once daily across a 21-day treatment cycle until loss of clinical benefit or unacceptable toxicity.
Active Comparator: Platinum-Based Chemotherapy Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).	Drug: Trastuzumab Subcutaneous (SC) Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months) Drug: Pertuzumab Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months) Drug: Carboplatin Carboplatin will be administered intravenously at the area under the curve (AUC) dose once every 3 weeks for up to 9 Cycles (Cycle = 21 days) in some combination with the following: Paclitaxel, Gemcitabine, Atezolizumab, Pertuzumab, and Trastuzumab SC. Drug: Paclitaxel Paclitaxel will be administered intravenously, 175 mg/m^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC Drug: Cisplatin Cisplatin will be administered intravenously, 60-75 mg/m^2, once every three weeks, for up to 9 cycles (Cycle = 21 days) in some combination with the following: Gemcitabine, Paclitaxel, Atezolizumab, Pertuzumab, and Trastuzumab SC. Drug: Gemcitabine Gemcitabine will be administered intravenously, 1000 mg/m^2, twice every three weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Cisplatin, Carboplatin, Atezolizumab, Pertuzumab, and Trastuzumab SC.

Arm

Intervention/Treatment

Experimental: Molecularly-Guided Therapy

Participants will be assigned to molecularly-guided therapy based on genomic profile.

Drug: Alectinib

Alectinib will be administered orally at the label-recommended dose (600 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).

Drug: Vismodegib

Vismodegib will be administered orally at the label-recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).

Drug: Ipatasertib

Ipatasertib will be administered orally at the label-recommended dose (400 mg) once daily on Days 1-21 of each 28-day Cycle in combination with paclitaxel, and as monotherapy after the final administration of paclitaxel, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).

Drug: Olaparib

Olaparib will be administered orally at the label-recommended dose (400 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).

Drug: Erlotinib

Erlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)

Drug: Bevacizumab

Bevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)

Drug: Vemurafenib

Vemurafenib will be administered orally, 960 mg twice daily, in combination with Cobimetinib, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)

Drug: Cobimetinib

Cobimetinib will be administered orally, 60mg once daily, in combination with Vemurafenib, on Days 1-21 of each 28-day Cycle, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)

Drug: Trastuzumab Subcutaneous (SC)

Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)

Drug: Pertuzumab

Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months)

Drug: Atezolizumab

Atezolizumab will be administered intravenously at the label-recommended dose (1200 mg), alone or in combination with chemotherapy, every 3 weeks until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).

Drug: Paclitaxel

Paclitaxel will be administered intravenously, 175 mg/m^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC

Drug: Entrectinib

Entrectinib will be administered orally at the label-recommended dose (600 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 60 months).

Drug: Ivosidenib

Ivosidenib will be administered orally at the label-recommended dose (500mg) once daily across a 28-day treatment cycle until loss of clinical benefit or unacceptable toxicity.

Drug: Pemigatinib

Pemigatinib will be administered orally at the label-recommended dose (13.5mg) once daily across a 21-day treatment cycle until loss of clinical benefit or unacceptable toxicity.

Active Comparator: Platinum-Based Chemotherapy

Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel).

Drug: Trastuzumab Subcutaneous (SC)

Drug: Pertuzumab

Drug: Carboplatin

Carboplatin will be administered intravenously at the area under the curve (AUC) dose once every 3 weeks for up to 9 Cycles (Cycle = 21 days) in some combination with the following: Paclitaxel, Gemcitabine, Atezolizumab, Pertuzumab, and Trastuzumab SC.

Drug: Paclitaxel

Drug: Cisplatin

Cisplatin will be administered intravenously, 60-75 mg/m^2, once every three weeks, for up to 9 cycles (Cycle = 21 days) in some combination with the following: Gemcitabine, Paclitaxel, Atezolizumab, Pertuzumab, and Trastuzumab SC.

Drug: Gemcitabine

Gemcitabine will be administered intravenously, 1000 mg/m^2, twice every three weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Cisplatin, Carboplatin, Atezolizumab, Pertuzumab, and Trastuzumab SC.

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS1) [From randomization to the first occurrence of disease progression as assessed by the investigator according to Response Evaluation Criteria In Solid Tumors v1.1 (RECIST v1.1) or death from any cause, through the end of study (approximately 60 months)]

Secondary Outcome Measures

Overall Survival (OS) [From randomization to death from any cause, through the end of study (approximately 60 months)]
Objective Response Rate (ORR1) [Two consecutive occurrences of complete or partial response >/=4 weeks apart]
Duration of Response (DOR1) [From the first documentation of a complete response (CR) or partial response (PR) to disease progression or death from any cause, whichever occurs first (up to approximately 60 months)]
Disease Control Rate (DCR1) [From randomization to death from any cause, through the end of study (approximately 60 months)]
Percentage of Participants with Adverse Events (AEs) [From baseline through the end of study (approximately 60 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically-confirmed unresectable cancer of unknown primary site (CUP) diagnosed according to criteria defined in the 2015 European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for CUP
No prior lines of systemic therapy for the treatment of CUP
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Candidate for platinum-based chemotherapy (according to the reference information for the intended chemotherapy)
At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
Formalin-Fixed Paraffin-Embedded (FFPE) tumor tissue sample </= 4 months old that is expected to be sufficient for generation of a comprehensive genomic profile at a central reference pathology laboratory

Exclusion Criteria:

Squamous cell CUP
Participants who can be assigned to a specific subset of CUP for which a specific treatment is recommended by the 2015 ESMO Clinical Practice Guidelines for CUP or with a clinical and IHC profile indicative of a specific primary tumor (favorable prognosis CUP subsets): Poorly differentiated carcinoma with midline distribution; women with papillary adenocarcinoma of the peritoneal cavity; women with adenocarcinoma involving only the axillary lymph nodes; squamous cell carcinoma of the cervical lymph nodes; poorly differentiated neuroendocrine tumors; men with blastic bone metastases and elevated prostate-specific antigen (PSA); participants with a single, small, potentially resectable tumor; colon cancer-type CUP, including participants with a CK7 negative, CK20 positive, CDX-2 positive immunohistochemistry profile; CK7-positive, CK20-negative and TTF-1 positive tumors in a context suggestive of lung adenocarcinoma or thyroid cancer; IHC profile definitely indicative of breast cancer OR an IHC profile indicative of breast cancer and either a history of breast cancer or lymph nodes in the drainage areas of the breast; high-grade serious carcinoma histology and elevated CA125 tumor marker and/or a mass in the gynecological tract or any tumor mass or lymph node in the abdominal cavity; IHC profile suggestive of renal cell carcinoma and renal lesions, with a Bosniak classification higher than IIF; IHC profile compatible with cholangiocarcinoma or pancreatobiliary (or upper gastrointestinal carcinoma) AND 1 or 2 liver lesions without extrahepatic disease or with only pulmonary metastases and/or lymph nodes in the drainage areas of the liver
Known presence of brain or spinal cord metastasis (including metastases that have been irradiated only)
Histology and immunohistology profiles (per 2015 ESMO guidelines) that are not adenocarcinoma or poorly differentiated carcinoma/adenocarcinoma
History or known presence of leptomeningeal disease
Known human immunodeficiency virus (HIV) infection
Significant cardiovascular disease
Prior allogeneic stem cell or solid organ transplantation
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or for up to 7 months after the final dose of treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blacktown Hospital	Blacktown	New South Wales	Australia	2148
2	Northern Cancer Institute	St Leonards	New South Wales	Australia	2065
3	Icon Cancer Foundation	South Brisbane	Queensland	Australia	4101
4	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
5	Peter MacCallum Cancer Center	North Melbourne	Victoria	Australia	3051
6	LKH-UNIV. KLINIKUM GRAZ; Klinische Abteilung für Onkologie	Graz		Austria	8036
7	Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.	Salzburg		Austria	5020
8	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Chemotherapie & Infektionskrankhei	Wien		Austria	1090
9	Hospital Sao Rafael - HSR	Salvador	BA	Brazil	41253-190
10	Instituto Nacional de Cancer - INCa; Oncologia	Rio de Janeiro	RJ	Brazil	20560-120
11	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS	Brazil	91350-200
12	Hospital de Cancer de Barretos	Barretos	SP	Brazil	14784-400
13	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP	Brazil	01246-000
14	Multiprofile Hospital for Active Treatment Uni Hospital; Department of medicinal oncology	Panagyurishte		Bulgaria	4500
15	Complex Oncology Center (COC)-Plovidiv	Plovdiv		Bulgaria	4000
16	MHAT Nadezhda	Sofia		Bulgaria	1330
17	MBAL Serdika EOOD	Sofia		Bulgaria	1632
18	Bradford Hill Centro de Investigaciones Clinicas; Bradford Hill Centro de Investigaciones Clinicas	Recoleta		Chile	8420383
19	James Lind Centro de Investigación Del Cáncer	Temuco		Chile	4800827
20	Clinica del Country	Bogota		Colombia	11001
21	Inst. Nacional de Cancerologia; Clinica de Seno	Bogota		Colombia	111511
22	Clínica Imbanaco; Oncology	Cali		Colombia
23	Fundacion Clinica Valle del Lili; Unidad de Investigaciones Clinicas	Cali		Colombia
24	Oncomedica S.A.	Monteria		Colombia	230002
25	Clinical Hospital Centre Zagreb	Zagreb		Croatia	10000
26	Bank of Cyprus Oncology Center	Nicosia		Cyprus	2006
27	Masarykuv onkologicky ustav	Brno		Czechia	656 53
28	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc		Czechia	779 00
29	Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika	Praha 2		Czechia	128 08
30	Aarhus Universitetshospital, Afdeling for Eksperimentel Klinisk Onkologi	Aarhus N		Denmark	8200
31	Rigshospitalet; Onkologisk Klinik	København Ø		Denmark	2100
32	North Estonia Medical Centre, Oncology and hematology Clinic; Department of Chemotherapy	Tallinn		Estonia	13419
33	Helsinki University Central Hospital; Dept of Oncology	Helsinki		Finland	00250
34	Tampere University Hospital; Dept of Oncology	Tampere		Finland	33520
35	Ico - Paul Papin	Angers		France	49000
36	CHRU Besançon	Besançon		France	25030
37	Institut Bergonie; Oncologie	Bordeaux		France	33076
38	CRLCC-Francois Baclesse; Oncologie Médicale	Caen		France	14076
39	Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne	Clermont-ferrand		France	63003
40	Centre Leon Berard	Lyon		France	69008
41	Institut Paoli-Calmettes; Oncologie Medicale 1	Marseille Cedex 09		France	13273
42	Institut régional du Cancer Montpellier	Montpellier		France	34298
43	Centre Antoine Lacassagne	Nice		France	06189
44	Institut Curie; Oncologie Medicale	Paris		France	75231
45	CHU Lyon - Centre Hospitalier Lyon Sud	Pierre-Benite (Lyon)		France	69495
46	Centre Eugene Marquis; Service d'oncologie	Rennes		France	35042
47	CHU Strasbourg - Hôpital Hautepierre	Strasbourg		France	67098
48	Hopital Foch; Oncologie	Suresnes		France	92151
49	Institut Gustave Roussy	Villejuif		France	94805
50	Universitätsklinikum Augsburg; II. Med. Klinik	Augsburg		Germany	86156
51	Charité-Universitätsm. Berlin; Med. Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunolo.	Berlin		Germany	10117
52	Onkologisches Zentrum - Onkologie Dachau	Dachau		Germany	85221
53	Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden	Dresden		Germany	01307
54	Universitätsklinikum Düsseldorf; Klinik für Hämatologie, Onkologie und Klinische Immunologie	Düsseldorf		Germany	40225
55	Kliniken Essen-Mitte, Evang. Huyssens-Stiftung, Klinik für Internistische Onkologie / Haematologie	Essen		Germany	45136
56	Universitätsklinikum Frankfurt, UCT; Universitäres Centrum für Tumorerkrankungen	Frankfurt		Germany	60590
57	Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum, Studienzentrale der II. Med. Klinik	Hamburg		Germany	20246
58	Praxis für Onkologie	Hannover		Germany	30449
59	Universitätsklinikum Heidelberg;Innere Medizin V, Hämatologie/Onkologie	Heidelberg		Germany	69120
60	SLK-Kliniken Heilbronn GmbH; Klinik für Innere Medizin III; Schwerpunkt Häma./Onko./Palliativm.	Heilbronn		Germany	74078
61	Universitätsklinikum Jena, Klinik für Innere Medizin II; Hämatologie und Internistische Onkologie	Jena		Germany	07747
62	Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik	Mainz		Germany	55131
63	Klinikum Mannheim III. Medizinische Klinik	Mannheim		Germany	68167
64	Klinikum der LMU München, Campus Großhadern, Krebszentrum München; Comprehensive Cancer Center LMU	München		Germany	81377
65	Universitätsklinikum Münster, Medizinische Klinik A, Translationale Onkologie	Münster		Germany	48149
66	RED-Oncology GmbH; Dres.Gerdt Hübner/Clemens Engels (Oldenburg)/Yael Bonnin-Gruber (Eutin)	Oldenburg / Holstein		Germany	23758
67	Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine	Athens		Greece	115 22
68	IASO General Hospital of Athens	Athens		Greece	155 62
69	Univ General Hosp Heraklion; Medical Oncology	Heraklion		Greece	711 10
70	Uni Hospital of Ioannina; Oncology Dept.	Ioannina		Greece	455 00
71	Theagenio Anticancer Hospital; 3Rd Oncology Clinic	Thessaloniki		Greece	546 39
72	Semmelweis Egyetem; Onkológiai Központ	Budapest		Hungary	1083
73	Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly	Budapest		Hungary	1122
74	Uzsoki Utcai Korhaz; Onkoradiológiai Osztály	Budapest		Hungary	1145
75	Debreceni Egyetem Klinikai Kozpont ; Department of Oncology	Debrecen		Hungary	4032
76	Bacs-Kiskun Megyei Korhaz, SZTE AOK Oktato Korhaza, Onkoradiologiai Kozpont	Kecskemet		Hungary	6000
77	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged		Hungary	6720
78	St Vincent'S Uni Hospital; Medical Oncology	Dublin		Ireland	4
79	Waterford Regional Hospital; Department Of Medical Oncology	Waterford		Ireland	X91 ER8E
80	Rabin MC; Davidof Center - Oncology Institute	Petach Tikva		Israel	4941492
81	Chaim Sheba medical center, Oncology division	Ramat Gan		Israel	5262000
82	Tel Aviv Sourasky Medical Ctr; Oncology	Tel Aviv		Israel	6423906
83	U. O. Oncologia Medica, Ospedale Santa Chiara	Pisa	Basilicata	Italy	56100
84	Policlinico Univ. - A.O. Mater Domini; U.O. Di Oncoematologia	Catanzaro	Calabria	Italy	88100
85	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania	Italy	80131
86	Arcispedale Santa Maria Nuova; Oncologia	Reggio Emilia	Emilia-Romagna	Italy	42100
87	Asst Papa Giovanni XXIII; Oncologia Medica	Bergamo	Lombardia	Italy	24127
88	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia	Italy	20132
89	Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck	Milano	Lombardia	Italy	20162
90	A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica	Orbassano	Piemonte	Italy	10043
91	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Sant'Andrea Delle Fratte (PG)	Umbria	Italy	06132
92	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima	Padova	Veneto	Italy	35128
93	Aichi Cancer Center	Aichi		Japan	464-8681
94	National Cancer Center Hospital East	Chiba		Japan	277-8577
95	National Hospital Organization Shikoku Cancer Center	Ehime		Japan	791-0280
96	National Hospital Organization Kyushu Cancer Center	Fukuoka		Japan	811-1395
97	The Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
98	Kazakh Scientific Research Institution Of Oncology and Radiology; Chemotherapy department	Almaty		Kazakhstan	050022
99	Multidisciplinary medical center; Chemotherapy department	Astana		Kazakhstan	010000
100	Seoul National University Hospital	Seoul		Korea, Republic of	03080
101	Asan Medical Center	Seoul		Korea, Republic of	05505
102	Samsung Medical Center	Seoul		Korea, Republic of	06351
103	Severance Hospital, Yonsei University Health System; Oncology	Seoul		Korea, Republic of	120-752
104	Riga East Clinical University Hospital Latvian Oncology Centre	Riga		Latvia	LV-1079
105	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)	Mexico	03100
106	Instituto Nacional de Cancerologia	Mexico City		Mexico	14080
107	AVIX Investigación Clínica S.C	Monterrey		Mexico	64710
108	Centro Oncologico Estatal ISSEMYM	Toluca		Mexico	50180
109	Erasmus MC	Rotterdam		Netherlands	3015 GD
110	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands	3584 CX
111	Ziekenhuis VieCuri Medisch Centrum	Venlo		Netherlands	5912 BL
112	Sørlandet Sykehus Kristiansand	Kristiansand		Norway	4604
113	Akershus universitetssykehus HF	Lørenskog		Norway	1478
114	Oslo universitetssykehus HF, Ullevål, Kreftsenteret	Oslo		Norway	0450
115	Helse Stavanger HF, Stavanger Universitetssjukehus; Klinikk for Blod og kreftsykdommer	Stavanger		Norway	4011
116	Hospital Nacional Cayetano Heredia; Hematology - Oncology	Lima		Peru	31
117	Oncosalud Sac; Oncología	Lima		Peru	41
118	Instituto Nacional de Enfermedades Neoplasicas	Lima		Peru	Lima 34
119	Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii	Kraków		Poland	30-688
120	Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz	Warszawa		Poland	02-781
121	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
122	Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj Napoca; Oncologie Medicala	Cluj Napoca		Romania	400015
123	Centrul de Oncologie Sfantul Nectarie	Craiova		Romania	200347
124	Institutul Regional de Oncologie Iasi; Clinica de Hematologie	Iasi		Romania	700483
125	Oncocenter Timisoara	Timişoara		Romania	300166
126	Hospital Sant Joan Despi- Moises Broggi; Servicio de Oncologia	Sant Joan Despí	Barcelona	Spain	08970
127	Hospital Quiron de Madrid; Servicio de Oncologia	Pozuelo de Alarcon	Madrid	Spain	28223
128	Complejo Hospitalario de Navarra; Servicio de Oncologia	Pamplona	Navarra	Spain	31008
129	Complexo Hospitalario de Vigo. Hospital Álvaro Cunqueiro; Servicio de Oncología	Vigo	Pontevedra	Spain	36312
130	Hospital Clínic i Provincial; Servicio de Oncología	Barcelona		Spain	08036
131	Institut Catala d Oncologia Hospital Duran i Reynals	Barcelona		Spain	08908
132	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid		Spain	28034
133	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid		Spain	28040
134	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
135	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga		Spain	29010
136	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla		Spain	41009
137	Hospital Universitari i Politecnic La Fe; Oncologia	Valencia		Spain	46026
138	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza		Spain	50009
139	Universitaetsspital Basel; Onkologie	Basel		Switzerland	4031
140	Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie	Chur		Switzerland	7000
141	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich		Switzerland	8091
142	Ramathibodi Hospital; Medicine/Oncology; Clinical Research Center	Bangkok		Thailand	10400
143	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok		Thailand	10700
144	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana		Turkey	01230
145	Ankara University Medical Faculty; Medikal Onkoloji	Ankara		Turkey	06100
146	Ankara Oncology Hospital; Oncology	Ankara		Turkey	06200
147	Akdeniz University Medical Faculty; Medical Oncology Department	Antalya		Turkey	07070
148	Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi	Edirne		Turkey	22030
149	Istanbul University Cerrahpaşa-Cerrahpaşa Medical Faculty; Medikal Onkoloji Departmani	Istanbul		Turkey	34098
150	İzmir Medical Park; Onkoloji	Izmır		Turkey	35575
151	Acıbadem Maslak Hastanesi Büyükdere	Sarıyer/İstanbul		Turkey	34457
152	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara		Turkey	06230
153	Royal United Hospital; Oncology Department	Bath		United Kingdom	BA1 3NG
154	Velindre Cancer Centre	Cardiff		United Kingdom	CF14 2TL
155	Western General Hospital; Edinburgh Cancer Center	Edinburgh		United Kingdom	EH4 2XU
156	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
157	University College London Hospitals NHS Foundation Trust - University College Hospital	London		United Kingdom	NW1 2PG
158	Hammersmith Hospital; Garry Weston Centre	London		United Kingdom	W12 0HS
159	Christie Hospital NHS Trust	Manchester		United Kingdom	M20 4BX
160	Freeman Hospital	Newcastle upon Tyne		United Kingdom	NE7 7DN
161	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
162	Torbay Hospital; Oncology Department	Torquay		United Kingdom	TQ27AA