PAPILLON: A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04538664

Collaborator

(none)

300

Enrollment

278

Locations

Arms

51.6

Anticipated Duration (Months)

1.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy, as demonstrated by progression-free survival (PFS), in participants treated with amivantamab in combination with chemotherapy, versus chemotherapy alone in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by EGFR Exon 20ins mutations.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Amivantamab Drug: Pemetrexed Drug: Carboplatin	Phase 3

Detailed Description

Lung cancer is one of the most common types of cancer and is the most common cause of death from cancer (almost 20 percent [%] of cancer deaths); NSCLC accounts for 80% to 85% of lung cancers. Amivantamab (JNJ-61186372) is a low fucose, fully human immunoglobulin G1 (IgG1)-based bispecific antibody directed against epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) tyrosine kinase receptors that is being developed for the treatment of solid tumors. The hypothesis is that amivantamab, when given in combination with standard of care carboplatin-pemetrexed chemotherapy, will prolong PFS compared with carboplatin-pemetrexed in patients with locally advanced or metastatic NSCLC characterized by EGFR Exon 20ins activating mutations. The study will include a Screening phase (28 days), a Treatment phase (from Cycle 1 Day 1 [21-day cycle] till end of treatment [30 days after last dose]) and a Follow up phase (from the end of treatment visit and until the end of study, death, loss to follow-up, or withdrawal of consent from participation in the study, whichever comes first). An independent data monitoring committee (IDMC) will be commissioned for the periodic review of safety and tolerability data, as well as planned efficacy analyses. Efficacy assessments will include disease assessment, symptomatic progression and patient-reported outcome. Safety assessments will include physical examinations, vital signs, electrocardiograms (ECGs), Eastern Cooperative Oncology Group (ECOG) performance status and clinical safety laboratory assessments (serum chemistry, hematology, coagulation, and urinalysis). The total duration of the study is up to 48 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Actual Study Start Date :

Oct 13, 2020

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Jan 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Amivantamab + Chemotherapy Participants will receive pemetrexed 500 milligram per meter square (mg/m^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is >=80 kilogram [kg]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is >=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3.	Drug: Amivantamab Amivantamab will be administered as an IV infusion at a dose of 1400 mg (1750 mg if body weight is >=80 kilogram [kg]) by once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is >=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3. Other Names: JNJ-61186372 Drug: Pemetrexed Pemetrexed will be administration as 500 mg/m^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and then as maintenance monotherapy until disease progression in Arms A and B. Drug: Carboplatin Carboplatin will be administration as AUC 5 IV infusion for up to 4 cycles on Day 1 of each 21-day cycle.
Experimental: Arm B: Chemotherapy Alone Participants will receive pemetrexed 500 mg/m^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin AUC 5 IV infusion will be administered on Day 1 of each 21-day cycle for up to 4 cycles.	Drug: Pemetrexed Pemetrexed will be administration as 500 mg/m^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and then as maintenance monotherapy until disease progression in Arms A and B. Drug: Carboplatin Carboplatin will be administration as AUC 5 IV infusion for up to 4 cycles on Day 1 of each 21-day cycle.

Arm

Intervention/Treatment

Experimental: Arm A: Amivantamab + Chemotherapy

Participants will receive pemetrexed 500 milligram per meter square (mg/m^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is >=80 kilogram [kg]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is >=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3.

Drug: Amivantamab

Amivantamab will be administered as an IV infusion at a dose of 1400 mg (1750 mg if body weight is >=80 kilogram [kg]) by once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is >=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3.

Other Names:

JNJ-61186372

Drug: Pemetrexed

Pemetrexed will be administration as 500 mg/m^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and then as maintenance monotherapy until disease progression in Arms A and B.

Drug: Carboplatin

Carboplatin will be administration as AUC 5 IV infusion for up to 4 cycles on Day 1 of each 21-day cycle.

Experimental: Arm B: Chemotherapy Alone

Participants will receive pemetrexed 500 mg/m^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin AUC 5 IV infusion will be administered on Day 1 of each 21-day cycle for up to 4 cycles.

Drug: Pemetrexed

Pemetrexed will be administration as 500 mg/m^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and then as maintenance monotherapy until disease progression in Arms A and B.

Drug: Carboplatin

Carboplatin will be administration as AUC 5 IV infusion for up to 4 cycles on Day 1 of each 21-day cycle.

Outcome Measures

Primary Outcome Measures

Progression-Free Survival (PFS) According to RECIST v1.1 as Assessed by Blinded Independent Central Review (BICR) [Up to 18 months]
PFS is defined as the time from randomization until the date of objective disease progression based on blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death (by any cause) in the absence of progression, whichever comes first.

Secondary Outcome Measures

Objective Response Rate (ORR) [Up to 48 months]
ORR is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as defined by BICR using RECIST v1.1 criteria.
Duration of Response (DoR) [Up to 48 months]
DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST v1.1 criteria.
Overall Survival (OS) [Up to 48 months]
Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.
Time to Subsequent Therapy (TST) [Up to 48 months]
TST is defined as the time from the date of randomization to the start date of the subsequent anti-cancer therapy following study treatment discontinuation, or death.
Progression-Free Survival After First Subsequent Therapy (PFS2) [Up to 48 months]
PFS2 is defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the primary variable PFS or death after starting the next line of treatment.
Time to Symptomatic Progression (TTSP) [Up to 48 months]
TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms.
Incidence and Severity of Adverse Events (AEs) [Up to 48 months]
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of Participants with Clinical Laboratory Abnormalities [Up to 48 months]
Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urine samples) will be reported.
Number of Participants with Vital Signs Abnormalities [Up to 48 months]
Number of participants with vital signs abnormalities (temperature, heart rate, respiratory rate, oxygen saturation, blood pressure) will be reported.
Number of Participants with Physical Examination Abnormalities [Up to 48 months]
Number of participants with physical examination abnormalities will be reported.
Serum Concentration of Amivantamab [Up to 48 months]
Serum samples will be analyzed to determine concentrations of amivantamab.
Number of Participants with Anti-Amivantamab Antibodies [Up to 48 months]
Number of participants with antibodies to amivantamab will be reported.
European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) [Up to 48 months]
The EORTC QLQ-C30 includes 30 items in 5 functional scales, 1 global health status scale, 3 symptom scales, and 6 single symptom items. The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.
Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) [Up to 48 months]
PROMIS-PF is used to characterize and better understand overall health, level of physical disability, and general well-being. Physical function is a foundation for commonly used general and cancer-specific patient reported outcomes (PRO) measures.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must have histologically or cytologically confirmed, locally advanced or metastatic, nonsquamous non-small cell lung cancer (NSCLC) with documented primary epidermal growth factor receptor (EGFR) Exon 20ins activating mutation
Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Participant must agree to genetic characterization of tumor status through the required pretreatment tumor biopsy (or submission of equivalent archival material), as well as baseline and periodic blood samples for analysis of tumor mutations in the bloodstream
A female participant of childbearing potential must have a negative serum or urine test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study

Exclusion Criteria:

Participant has evidence of synchronous NSCLC disease (as suggested by genetic characterization or radiographic appearance)
Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to randomization is eligible)
Participant has history of spinal cord compression that has not been treated definitively with surgery or radiation
Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD, or radiation pneumonitis
Participant has a contraindication to the use of carboplatin or pemetrexed (refer to local prescribing information for each agent). Participant has a history of hypersensitivity to, or cannot take, vitamin B12 or folic acid

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yuma Regional Medical Center	Yuma	Arizona	United States	85364
2	City of Hope	Duarte	California	United States	91010
3	City of Hope	Duarte	California	United States	91010
4	Compassionate Cancer Care	Fountain Valley	California	United States	92708
5	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
6	University of California, Irvine	Orange	California	United States	92868
7	UCLA	Santa Monica	California	United States	90404
8	University of Colorado	Aurora	Colorado	United States	80045
9	Georgetown University Hospital	Washington	District of Columbia	United States	20007
10	Mayo Clinic	Jacksonville	Florida	United States	32224
11	Ocala Oncology Center	Ocala	Florida	United States	34474
12	H. Lee Moffitt Cancer & Research Institute	Tampa	Florida	United States	33612
13	University Cancer & Blood Center, LLC	Athens	Georgia	United States	30607
14	Hawaii Cancer Care	Honolulu	Hawaii	United States	96813
15	Illinois Cancer Care	Peoria	Illinois	United States	61615
16	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46825
17	Beacon Medical Group Clinical Research	South Bend	Indiana	United States	46601
18	Pontchartrain Cancer Center	Covington	Louisiana	United States	70433
19	East Jefferson General Hospital	Metairie	Louisiana	United States	70006
20	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
21	Frederick Health Hospital - James M Stockman Cancer Institute	Frederick	Maryland	United States	21702-4337
22	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
23	Henry Ford Hospital	Detroit	Michigan	United States	48202
24	Mayo Clinic	Rochester	Minnesota	United States	55905
25	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
26	Central Care Cancer Center	Bolivar	Missouri	United States	65613
27	Washington University Medical Center	Saint Louis	Missouri	United States	63110
28	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
29	Essex Oncology of North Jersey	Belleville	New Jersey	United States	07109
30	Regional Cancer Care Associates LLC	East Brunswick	New Jersey	United States	08816
31	Langone Health at NYC University, NYU School of Medicine	New York	New York	United States	10016
32	Icahn School of Medicine at Mt. Sinai	New York	New York	United States	10029
33	Columbia University Medical Center	New York	New York	United States	10032
34	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
35	Durham VAMC	Durham	North Carolina	United States	27705
36	TriHealth Network	Cincinnati	Ohio	United States	45220
37	Cleveland Clinic	Cleveland	Ohio	United States	44195
38	Ohio Health	Columbus	Ohio	United States	43214
39	Oklahoma Cancer Specialists and Research Institute, LLC	Tulsa	Oklahoma	United States	74146
40	Providence Portland Medical Center	Portland	Oregon	United States	97213
41	Sanford Health	Sioux Falls	South Dakota	United States	57104
42	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
43	UT Southwestern Medical Center	Dallas	Texas	United States	75390
44	Oncology Consultants - Texas	Houston	Texas	United States	77030
45	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
46	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
47	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
48	NorthWest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
49	Chris O'Brien Lifehouse	Camperdown		Australia	2050
50	Austin Hospital	Heidelberg		Australia	3084
51	St George Hospital	Kogarah		Australia	2217
52	Cabrini Medical Centre	Malvern		Australia	3144
53	Sir Charles Gairdner Hospital	Nedlands		Australia	6009
54	UZ Leuven	Leuven		Belgium	3000
55	Algemeen Ziekenhuis Delta	Roeselare		Belgium	8800
56	CHU UCL Namur - Site Godinne	Yvoir		Belgium	5530
57	Fundacao Pio Xii - Hospital De Cancer De Barretos	Barretos		Brazil	14784-400
58	Cetus Oncologia	Belo Horizonte		Brazil	30110-017
59	Hospital Evangélico de Cachoeiro de Itapemirim	Cachoeiro de Itapemirim		Brazil	29308020
60	Ynova Pesquisa Clinica	Florianopolis		Brazil	88020-210
61	Hospital de Caridade de Ijui	Ijuí		Brazil	98700-000
62	Liga Norte Riograndense Contra O Cancer	Natal		Brazil	59062-000
63	UPCO Unidade de Pesquisa Clinica em Oncologia	Pelotas		Brazil	96020 080
64	Santa Casa de Misericordia de Porto Alegre	Porto Alegre		Brazil	90020-090
65	Centro de Pesquisa em Oncologia - PUCRS	Porto Alegre		Brazil	90610 000
66	INCA - Instituto Nacional Do Cancer	Rio de Janeiro		Brazil	20231-050
67	Oncoclínicas	Rio de Janeiro		Brazil	22250 905
68	Instituto D'Or de Pesquisa e Ensino (IDOR)	Rio de Janeiro		Brazil	22281-100
69	Fundação Antônio Prudente - A.C. Camargo Cancer Center	Sao Paulo		Brazil	01509-010
70	Núcleo de Pesquisa São Camilo	Sao Paulo		Brazil	04014-002
71	IOS - Instituto de Oncologia de Sorocaba Dr. Gilson Delgado	Sorocaba		Brazil	18030-075
72	Instituto do Cancer do Estado de Sao Paulo ICESP	São Paulo		Brazil	01246-000
73	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
74	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
75	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
76	University Health Network	Toronto	Ontario	Canada	M5G 2C4
77	McGill University Health Centre	Montreal	Quebec	Canada	H4A 3J1
78	Beijing Cancer Hospital	Beijing		China	100142
79	Chinese PLA General Hospital	Beijing		China	100853
80	Beijing Chest hospital, Capital medical university	Beijing		China	101199
81	Peking University International Hospital	Beijing		China	102206
82	Jilin cancer hospital	Changchun		China	130000
83	Hunan Cancer hospital	Changsha		China	410013
84	The First People's Hospital Of Changzhou	Changzhou		China	213003
85	West China Hospital, Sichuan University	Chengdu		China	610041
86	Chongqing University Cancer Hospital	Chongqing		China	400030
87	Fujian Medical University Union Hospital	Fuzhou		China	350001
88	The First Affiliated Hospital, Sun Yat-sen University	Guang Zhou		China	510080
89	Zhejiang Cancer Hospital	Hang Zhou		China	310022
90	The First Affiliated Hospital, Zhejiang University College of Medicine	Hangzhou		China	310003
91	The Second Affiliated Hospital of Zhejiang University College of Medicine	Hangzhou		China	310009
92	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou		China	310016
93	Harbin medical university cancer hospital	Harbin		China	150081
94	Taizhou Hospital of Zhejiang Province	Linhai		China	317000
95	Nanjing Drum Tower Hospital	Nanjing		China	210031
96	Shanghai Chest Hospital	Shanghai		China	200030
97	Fudan University Shanghai Cancer Center	Shanghai		China	200032
98	Shanghai Zhongshan Hospital	ShangHai		China	200032
99	Shanghai East Hospital	Shanghai		China	200123
100	Shanghai Pulmonary Hospital	Shanghai		China	200433
101	Shengjing Hospital of China Medical University	Shenyang		China	110004
102	Cancer hospital Chinese Academy of Medical Sciences, Shenzhen Center	Shenzhen		China	518116
103	Tianjin Medical University General Hospital	Tianjin		China	300052
104	Weifang People's Hospital	Weifang		China	261000
105	TongJi Hospital of TongJi Medical College of Huazhong University of Science & Technology	Wuhan		China	430030
106	Hospital of Jiangnan University	Wuxi		China	214122
107	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an		China	710061
108	Yantai Yuhuangding Hospital	Yantai		China	264000
109	Henan Cancer Hospital	Zhengzhou		China	450008
110	Institut Bergonié	Bordeaux		France	33000
111	Hospices Civils de Lyon HCL	Bron		France	69500
112	Centre Georges François Leclerc	Dijon		France	21000
113	Centre Hospitalier Le Mans	le mans Cedex 9		France	72037
114	CHR Hôpital Calmette	Lille CEDEX		France	59037
115	CHU Nantes - Hopital Nord Laënnec	NANTES cedex 1		France	44093
116	Institut Curie	Paris		France	75005
117	CHU Bordeaux	Pessac		France	33604
118	HIA Begin	Saint Mande		France	94163
119	Zentralklinik Bad Berka GmbH	Bad Berka		Germany	99437
120	Evangelische Lungenklinik Berlin	Berlin		Germany	13125
121	Asklepios Klinik Gauting GmbH - Asklepios Fachkliniken München-Gauting	Gauting		Germany	82131
122	Thoraxklinik am Universitätsklinikum Heidelberg	Heidelberg		Germany	69126
123	Onkologische Schwerpunktpraxis	Heilbronn		Germany	74072
124	Lungenklinik Hemer	Hemer		Germany	58675
125	Universitaetsklinikum Koeln	Koeln		Germany	50937
126	Kliniken der Stadt Koeln gGmbH	Koeln		Germany	51109
127	Bethanien Krankenhaus	Moers		Germany	47441
128	Pius-Hospital Oldenburg	Oldenburg		Germany	26121
129	Oncologianova GmbH	Recklinghausen		Germany	45659
130	Orszagos Koranyi Tbc es Pulmonologiai Intezet	Budapest		Hungary	H-1529
131	Veszprém Megyei Tudőgyógyintézet	Farkasgyepü		Hungary	8582
132	Mátrai Gyógyintézet-Bronchológia	Gyöngyös		Hungary	3233
133	Fejer Megyei Szent Gyorgy Egyetemi Oktatokorhaz	Szekesfehervar		Hungary	8000
134	Markusovszky Egyetemi Oktatokorhaz	Szombathely		Hungary	9700
135	Tudogyogyintezet Torokbalint	Torokbalint		Hungary	2045
136	Basavatarakam Indo-American Hospital	Hyderabad		India	500034
137	Tata Medical Center	Kolkata		India	700160
138	Tata Memorial Hospital	Mumbai		India	400012
139	HCG Manavta Cancer Centre	Nasik		India	422002
140	Rajiv Gandhi Cancer Institute & Research Centre	New Delhi		India	110085
141	Noble Hospital Pvt Ltd	Pune		India	411013
142	Soroka Medical Center	Beersheba		Israel	85101
143	Shaare Zedek Medical Center	Jerusalem		Israel	91031
144	Hadassah Medical Center	Jerusalem		Israel	9112001
145	Meir Medical Center	Kfar Saba		Israel	44281
146	Rabin Medical Center	Petah Tikva		Israel	49100
147	Tel-Aviv Sourasky Medical Center	Tel-Aviv		Israel	6423906
148	A.O.U Sant'Orsola-Malpighi	Bologna		Italy	40138
149	Azienda Ospedaliero Univ. Policlinico Gaspare Rodolico	Catania		Italy	95123
150	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola		Italy	47014
151	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano		Italy	20122
152	IRCCS Ospedale San Raffaele	Milano		Italy	20132
153	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
154	San Gerardo Hospital	Monza		Italy	20052
155	Ospedale S. Maria Delle Croci	Ravenna		Italy	48121
156	Irccs Gemelli	Roma		Italy	00168
157	Istituto Clinico Humanitas	Rozzano		Italy	20089
158	Juntendo University Hospital	Bunkyo-Ku		Japan	113-8431
159	Osaka Habikino Medical Center	Habikino		Japan	583-8588
160	Saitama Medical University International Medical Center	Hidaka		Japan	350-1298
161	National Hospital Organization Himeji Medical Center	Himeji		Japan	670-8520
162	Kansai Medical University Hospital	Hirakata		Japan	573-1191
163	Hyogo Cancer Center	Hyogo		Japan	673-8558
164	Kanazawa University Hospital	Kanazawa		Japan	920-8641
165	National Cancer Center Hospital East	Kashiwa		Japan	277-8577
166	Kishiwada City Hospital	Kishiwada		Japan	596-8501
167	Kobe City Medical Center General Hospital	Kobe		Japan	650-0047
168	Kurashiki Central Hospital	Kurashiki		Japan	710-8602
169	Kurume University Hospital	Kurume		Japan	830-0011
170	Matsusaka Municipal Hospital	Matsusaka		Japan	515-8544
171	National Hospital Organization Nagoya Medical Center	Nagoya-shi		Japan	460-0001
172	Aichi Cancer Center Hospital	Nagoya-Shi		Japan	464-8681
173	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
174	Kindai University Hospital	Osaka-Sayama-shi		Japan	589-8511
175	Kitasato University Hospital	Sagamihara		Japan	252-0375
176	Hokkaido University Hospital	Sapporo-shi		Japan	060-8648
177	Iwate Medical University Hospital	Shiwa-gun		Japan	028-3695
178	Shizuoka Cancer Center	Shizuoka		Japan	411-8777
179	The Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
180	Ehime University Hospital	Toon-shi		Japan	791-0295
181	Wakayama Medical University Hospital	Wakayama		Japan	641-8510
182	National Hospital Organization Yamaguchi Ube Medical Center	Yamaguchi		Japan	755-0241
183	Inje University Haeundae Paik Hospital	Busan		Korea, Republic of	48108
184	National Cancer Center	Gyeonggi-do		Korea, Republic of	10408
185	Seoul National University Bundang Hospital	Gyeonggi-do		Korea, Republic of	13620
186	GyeongSang National University Hospital	Gyeongsangnam-do		Korea, Republic of	52727
187	Chonnam National University Hwasun Hospital	Jeollanam-do		Korea, Republic of	58128
188	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
189	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	03181
190	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
191	Asan Medical Center	Seoul		Korea, Republic of	05505
192	Samsung Medical Center	Seoul		Korea, Republic of	06351
193	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
194	Hospital Pulau Pinang	George Town		Malaysia	10990
195	Hospital Sultan Ismail	Johor Bahru		Malaysia	81100
196	Hospital Kuala Lumpur	Kuala Lumpur		Malaysia	50586
197	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
198	Centro Oncológico de Chihuahua	Chihuahua		Mexico	31217
199	Mexico Centre for Clinical Research, S.A. de C.V.	Ciudad de Mexico		Mexico	03100
200	Médica Sur	Ciudad de Mexico		Mexico	14050
201	Instituto Nacional de Cancerologia	Ciudad de Mexico		Mexico	14080
202	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara		Mexico	44280
203	Health Pharma Professional Research	Mexico		Mexico	03100
204	i Can Oncology Center	Monterrey		Mexico	64710
205	Oncologia Integral Satelite	Naucalpan		Mexico	53100
206	Centrum Onkologii im. Prof. F. Lukaszczyka	Bydgoszcz		Poland	85-796
207	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-214
208	Szpitale Pomorskie Sp. z o.o.	Gdynia		Poland	81-519
209	Warminsko-Mazurskie Centrum Chorob Pluc w Olsztynie	Olsztyn		Poland	10-357
210	Private Specialist Hospitals - MedPolonia	Poznan		Poland	60-693
211	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa		Poland	02-781
212	Centro Hospitalar e Universitário de Coimbra, EPE	Coimbra		Portugal	3045 - 081
213	Fundação Champalimaud	Lisboa		Portugal	1400-038
214	Hosp. Cuf Descobertas	Lisboa		Portugal	1998-018
215	Chlc - Hosp. Sto Antonio Dos Capuchos	Lisboa		Portugal	G1R 2J6
216	Centro Hospitalar Universitario do Porto, EPE	Porto		Portugal	4099-001
217	Instituto Portugues de Oncologia	Porto		Portugal	4200-072
218	Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.	Vila Nova de Gaia		Portugal	4434-502
219	Pan American Center for Oncology Trials LLC	Rio Piedras		Puerto Rico	00935
220	Irkutsk Regional Oncology Dispensary	Irkutsk		Russian Federation	664035
221	State Medical Institution 'Republican Clinical Oncological Centre' at Republic of Tatarstan	Kazan		Russian Federation	420029
222	Moscow City Oncology Hospital № 62	Krasnogorsk		Russian Federation	143423
223	Krasnoyarsk Regional Oncology Dispensary	Krasnoyarsk		Russian Federation	660133
224	Leningrad Regional Oncology Dispensary	Kuzmolovsky		Russian Federation	188663
225	Moscow Oncology Research Center n.a. Blokhin	Moscow		Russian Federation	115478
226	MCK	Moscow		Russian Federation	115533
227	Central Clinical Hospital	Moscow		Russian Federation	121359
228	City Clinical Hospital #1	Nalchik		Russian Federation	360000
229	Nizhny Novgorod Regional Oncological Dispensary	Nizhniy Novgorod		Russian Federation	603000
230	N.N. Petrov Research Institute Of Oncology	Saint Petersburg		Russian Federation	197758
231	Leningrad Regional Clinical Hospital	Saint-Petersburg		Russian Federation	194291
232	Oncology Medical Clinics AV Medical group	St-Petersburg		Russian Federation	196006
233	City Clinical Oncology Dispensary	St. Petersburg		Russian Federation	198255
234	Tomsk Cancer Research Institute	Tomsk		Russian Federation	634050
235	Bashkir State Medical University	Ufa		Russian Federation	450083
236	Yaroslavl Regional Clinical Oncology Hospital	Yaroslavl		Russian Federation	150054
237	Hosp. Univ. A Coruña	A Coruña		Spain	15006
238	Inst. Cat. D'Oncologia-Badalona	Badalona		Spain	08916
239	Hosp. de La Santa Creu I Sant Pau	Barcelona		Spain	08025
240	Hosp. Univ. Quiron Dexeus	Barcelona		Spain	08028
241	Hosp. Univ. Vall D Hebron	Barcelona		Spain	08035
242	Hosp. Univ. de Burgos	Burgos		Spain	09006
243	Hosp. Gral. Univ. Gregorio Marañon	Madrid		Spain	28007
244	Hosp. Univ. Ramon Y Cajal	Madrid		Spain	28034
245	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
246	Hosp. Univ. La Paz	Madrid		Spain	28046
247	Hosp. Univ. Pta. de Hierro Majadahonda	Majadahonda		Spain	28222
248	Hosp. Virgen de La Victoria	Málaga		Spain	29010
249	Clinica Univ. de Navarra	Pamplona		Spain	31008
250	Hosp. Virgen Del Rocio	Seville		Spain	41013
251	Hosp. Clinico Univ. Lozano Blesa	Zaragoza		Spain	50009
252	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung		Taiwan	807
253	Chang Gung Medical Foundation	Kaohsiung		Taiwan	833
254	Taipei Medical University Shuang Ho Hospital	New Taipei		Taiwan	23561
255	Chung Shan Medical University Hospital	Taichung		Taiwan	402
256	China Medical University Hospital	Taichung		Taiwan	40447
257	National Taiwan University Hospital	Taipei City		Taiwan	10002
258	Phramongkutklao Hospital and Medical College	Bangkok		Thailand	10400
259	Siriraj Hospital	Bangkok		Thailand	10700
260	Songklanagarind Hospital, Prince of Songkla University	Songkla		Thailand	90110
261	Adana City Hospital	Adana		Turkey	01060
262	Başkent University Medical Faculty Adana Application and Research Center	Adana		Turkey	01250
263	Gazi University Hospital	Ankara		Turkey	6560
264	Ankara Bilkent City Hospital	Ankara		Turkey	6800
265	Trakya University Medical Faculty	Edirne		Turkey	22030
266	Istanbul Universitesi Cerrahpasa Tip Fakultesi Ic Hastaliklari Anabilim Dali Medikal Onkoloji Bd	Istanbul		Turkey	34098
267	Medipol Mega University Hospital	Istanbul		Turkey	34214
268	Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi	Istanbul		Turkey	34722
269	Izmir Medical Park Hospital	Izmir		Turkey	35580
270	Dnipropetrovsk State Medical Academy, Dnipropetrovsk City Multifield Clinical Hospital # 4	Dnipro		Ukraine	49102
271	Medical Center 'Ok Clinic' of LLC 'International Institute of Clinical Studies'	Kyiv		Ukraine	02091
272	National Cancer Institute	Kyiv		Ukraine	03022
273	Municipal Institution 'Odesa Clinical Oncology Dispensary'	Odesa		Ukraine	65010
274	Municipal Oncology Centre of Uzhgorod Central Municipal Clinical Hospitlal	Uzhgorod		Ukraine	88000
275	Edinburgh Cancer Centre Western General	Edinburgh		United Kingdom	EH4 2XU
276	The Royal Marsden NHS Trust	London		United Kingdom	SW3 6JJ
277	Nottingham University Hospitals NHS Trust	Nottingham		United Kingdom	NG5 1PB
278	The Royal Marsden NHS Trust	Sutton		United Kingdom	SM2 5PT