Spotlight: A Phase 3 Efficacy, Safety and Tolerability Study of Zolbetuximab (Experimental Drug) Plus mFOLFOX6 Chemotherapy Compared to Placebo Plus mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction (GEJ) Cancer

Sponsor

Astellas Pharma Global Development, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03504397

Collaborator

(none)

566

Enrollment

220

Locations

Arms

75.3

Anticipated Duration (Months)

2.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A study of zolbetuximab (IMAB362) plus mFOLFOX6 versus placebo plus mFOLFOX6 in subjects with Claudin 18.2 positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

Why is this study being done?

SPOTLIGHT is a new clinical study for adult patients who have any of:

advanced unresectable gastric or GEJ cancer
metastatic gastric or GEJ cancer These types of cancers have a unique set of proteins (called Claudin 18.2). We may be able to use a treatment that targets the proteins to kill the cancer cells.

For patients with one of the types of cancer listed above, mFOLFOX6 (a combination of three chemotherapies known as Oxaliplatin, Leucovorin, and Fluorouracil) is a current treatment option. This study is testing an experimental medicine called zolbetuximab (IMAB362). Zolbetuximab attaches itself to Claudin 18.2 on the cancer cells causing cancer cell death.

Patients will be assigned to one of two groups by chance and given either:

zolbetuximab with mFOLFOX6; or
a placebo with mFOLFOX6 A placebo is a treatment that looks like the experimental medicine, but contains no medicine.

The goal of the study is to find out if zolbetuximab with mFOLFOX6 helps patients to live longer by stopping the cancer from getting worse.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer Metastatic Gastric Adenocarcinoma or Cancer Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma	Drug: zolbetuximab Drug: placebo Drug: oxaliplatin Drug: folinic acid Drug: fluorouracil	Phase 3

Detailed Description

The study consists of the following periods: screening; treatment; post-treatment follow up, safety follow up, long term and survival follow-up.

Study Design

Study Type:

Interventional

Actual Enrollment :

566 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared With Placebo Plus mFOLFOX6 as First-line Treatment of Subjects With Claudin (CLDN)18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

Actual Study Start Date :

Jun 21, 2018

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Sep 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (zolbetuximab plus mFOLFOX6) Participants will receive a loading dose of zolbetuximab at Cycle 1 Day 1 followed by a lower dose in subsequent cycles every 3 weeks. Additionally, participants will receive up to 12 treatments of mFOLFOX6 (or components of mFOLFOX6 if some components are discontinued due to toxicity) over 4 or more cycles (each cycle is approximately 42 days) in which mFOLFOX6 is administered on Days 1, 15 and 29. After 12 mFOLFOX6 treatments, participants may continue to receive fluorouracil (5-FU) and folinic acid at the investigator's discretion until the subject meets study treatment discontinuation criteria.	Drug: zolbetuximab Zolbetuximab will be administered as a minimum 2-hour IV infusion. Other Names: IMAB362 Drug: oxaliplatin Oxaliplatin will be administered as a 2-hour IV infusion Drug: folinic acid Folinic acid will be administered as a 2-hour IV infusion. Drug: fluorouracil Fluorouracil will be administered as IV bolus over 5-15 minutes and continuous IV infusion over 46-48 hours.
Placebo Comparator: Arm B (Placebo plus mFOLFOX6) Participants will receive placebo starting at Cycle 1 Day 1 and every 3 weeks thereafter. Additionally, participants will receive up to 12 treatments of mFOLFOX6 (or components of mFOLFOX6 if some components are discontinued due to toxicity) over 4 or more cycles (each cycle is approximately 42 days) in which mFOLFOX6 is administered on Days 1, 15 and 29. After 12 mFOLFOX6 treatments, participants may continue to receive fluorouracil (5-FU) and folinic acid at the investigator's discretion until the subject meets study treatment discontinuation criteria.	Drug: placebo Placebo will be administered as a minimum 2-hour IV infusion. Drug: oxaliplatin Oxaliplatin will be administered as a 2-hour IV infusion Drug: folinic acid Folinic acid will be administered as a 2-hour IV infusion. Drug: fluorouracil Fluorouracil will be administered as IV bolus over 5-15 minutes and continuous IV infusion over 46-48 hours.

Arm

Intervention/Treatment

Experimental: Arm A (zolbetuximab plus mFOLFOX6)

Participants will receive a loading dose of zolbetuximab at Cycle 1 Day 1 followed by a lower dose in subsequent cycles every 3 weeks. Additionally, participants will receive up to 12 treatments of mFOLFOX6 (or components of mFOLFOX6 if some components are discontinued due to toxicity) over 4 or more cycles (each cycle is approximately 42 days) in which mFOLFOX6 is administered on Days 1, 15 and 29. After 12 mFOLFOX6 treatments, participants may continue to receive fluorouracil (5-FU) and folinic acid at the investigator's discretion until the subject meets study treatment discontinuation criteria.

Drug: zolbetuximab

Zolbetuximab will be administered as a minimum 2-hour IV infusion.

Other Names:

IMAB362

Drug: oxaliplatin

Oxaliplatin will be administered as a 2-hour IV infusion

Drug: folinic acid

Folinic acid will be administered as a 2-hour IV infusion.

Drug: fluorouracil

Fluorouracil will be administered as IV bolus over 5-15 minutes and continuous IV infusion over 46-48 hours.

Placebo Comparator: Arm B (Placebo plus mFOLFOX6)

Participants will receive placebo starting at Cycle 1 Day 1 and every 3 weeks thereafter. Additionally, participants will receive up to 12 treatments of mFOLFOX6 (or components of mFOLFOX6 if some components are discontinued due to toxicity) over 4 or more cycles (each cycle is approximately 42 days) in which mFOLFOX6 is administered on Days 1, 15 and 29. After 12 mFOLFOX6 treatments, participants may continue to receive fluorouracil (5-FU) and folinic acid at the investigator's discretion until the subject meets study treatment discontinuation criteria.

Drug: placebo

Placebo will be administered as a minimum 2-hour IV infusion.

Drug: oxaliplatin

Oxaliplatin will be administered as a 2-hour IV infusion

Drug: folinic acid

Folinic acid will be administered as a 2-hour IV infusion.

Drug: fluorouracil

Fluorouracil will be administered as IV bolus over 5-15 minutes and continuous IV infusion over 46-48 hours.

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [Up to 13 months]
PFS is defined as the time from the date of randomization until the date of radiological progressive disease (per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 by Independent Review Committee (IRC)) or death from any cause, whichever is earliest.

Secondary Outcome Measures

Overall Survival (OS) [Up to 23 months]
OS is defined as the time from the date of randomization until the date of death from any cause.
Objective Response Rate (ORR) [Up to 13 months]
ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by Independent Review Committee (IRC) per RECIST 1.1.
Duration Of Response (DOR) [Up to 13 months]
DOR, defined as the time from the date of the first response (CR/PR) until the date of progressive disease as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest.
Safety and tolerability assessed by adverse events (AEs) [Up to 16 months]
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Number of participants with laboratory assessments abnormalities and or adverse events [Up to 14 months]
Number of participants with potentially clinically significant laboratory values.
Number of participants with vital signs abnormalities and or adverse events [Up to 14 months]
Number of participants with potentially clinically significant vital sign values.
Number of participants with electrocardiograms (ECG) abnormalities and or adverse events [Up to 14 months]
Number of participants with potentially clinically significant ECG values.
Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities and or adverse events [Up to 13 months]
Number of participants with potentially clinically significant ECOG performance status values. ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.
Health Related Quality of Life (HRQoL) measured by the European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30) questionnaire [Up to 16 months]
The EORTC-QLQ-C30 is a cancer-specific instrument consisting of 5 functional domain scales: physical, role, emotional, social and cognitive.
HRQoL measured by the QLQ-OG25 questionnaire [Up to 16 months]
The EORTC-QLQ-OG25 instrument evaluates Gastric and GEJ cancer-specific symptoms such as stomach discomfort, difficulties eating and swallowing and indigestion.
HRQoL measured by the Global Pain (GP) questionnaire [Up to 16 months]
The GP instrument is a single assessment of overall pain.
HRQoL measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) questionnaire [Up to 16 months]
The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.
Time to confirmed deterioration (TTCD) [Up to 16 months]
Calculated using the physical function (PF), OG25-Pain and Global Health Status (GHS)/QoL scores as measured by EORTC QLQ-C30 and QLQ-OG25. TTCD is defined as time to first confirmed deterioration (time from randomization to first clinically meaningful deterioration that is confirmed at the next scheduled visit).
PK of zolbetuximab: Concentration Immediately Prior to Dosing at multiple dosing (Ctrough) [Up to 16 months]
Ctrough will be derived from the PK serum samples collected.
Number of anti-drug antibody (ADA) Positive Participants [Up to 16 months]
Immunogenicity will be measured by the number of participants that are ADA positive.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Female subject eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin and a demonstrated non-pregnant status through additional testing are eligible) and at least one of the following conditions applies:
Not a woman of child-bearing potential (WOCBP) OR
WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs
Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
A sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug administration.
Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen.
Subject has ECOG performance status 0 to 1.
Subject has predicted life expectancy ≥ 12 weeks.
Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
Hemoglobin (Hgb) ≥ 9 g/dL. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL.
Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
Platelets ≥ 100 x 10^9/L
Albumin ≥ 2.5 g/dL
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or < 3.0 x ULN if liver metastases are present)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
Estimated creatinine clearance ≥ 30 mL/min
Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)

Exclusion Criteria:

Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies, as long as it was completed at least 6 months prior to randomization. Subject may have received treatment with herbal medications that have known antitumor activity > 28 days prior to randomization.
Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
Subject has received other investigational agents or devices within 28 days prior to randomization.
Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
Subject has prior severe allergic reaction or intolerance to any component of mFOLFOX6.
Subject has known dihydropyrimidine dehydrogenase deficiency.
Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
Subject has significant gastric bleeding and/or untreated gastric ulcers that would exclude the subject from participation.
Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen (HBs Ag)) or C infection. NOTE: Screening for these infections should be conducted per local requirements.
For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded.
Subjects with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test are eligible.
Subjects treated for HCV with undetectable viral load results are eligible.
Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
Subject has significant cardiovascular disease, including any of the following:
Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident (CVA) or hypertensive crisis within 6 months prior to randomization.
History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes)
QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects
History or family history of congenital long QT syndrome
Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible).
Subject has a history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.
Subject has known peripheral sensory neuropathy > Grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
Subject has had a major surgical procedure ≤ 28 days prior to randomization.
Subject is without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
Subject has psychiatric illness or social situations that would preclude study compliance.
Subject has another malignancy for which treatment is required.
Subject has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona	Phoenix	Arizona	United States	85004
2	The University of Arizona Medical Center	Tucson	Arizona	United States	85724
3	CBCC Global Research, Inc. at Comprehensive Blood and Cancer	Bakersfield	California	United States	93309
4	City of Hope Nat'l Medical Center	Duarte	California	United States	91010
5	St. Jude Hospital Yorba Linda	Fullerton	California	United States	92835
6	Pacific Shores Medical Group	Huntington Beach	California	United States	92648
7	Loma Linda University	Loma Linda	California	United States	92354
8	The Angeles Clinic and Research Institute	Los Angeles	California	United States	90025
9	University of California Davis	Sacramento	California	United States	95817
10	University of California - San Francisco	San Francisco	California	United States	94143
11	University of Colorado	Aurora	Colorado	United States	80045
12	Memorial Sloan Kettering Cancer Center	Middletown	Connecticut	United States	07748-3052
13	Memorial Cancer Institute - West	Hollywood	Florida	United States	33021
14	University of Miami	Miami	Florida	United States	33136
15	Orlando Health Inc	Orlando	Florida	United States	32806
16	Memorial Hospital West	Pembroke Pines	Florida	United States	33028
17	Cancer Treatment Centers of America, Atlanta	Newnan	Georgia	United States	30265
18	Northwestern University Medical Center	Chicago	Illinois	United States	60611
19	University of Chicago	Chicago	Illinois	United States	60637
20	Norton Cancer Institute	Louisville	Kentucky	United States	40217
21	University of Maryland Medical Center(UMMC)Transplant Center	Baltimore	Maryland	United States	21201
22	Maryland Oncology Hematology	Brandywine	Maryland	United States	20613
23	Massachusetts General Hospital	Boston	Massachusetts	United States	02114-2696
24	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
25	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
26	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
27	Health Partners Institute	Saint Louis Park	Minnesota	United States	55426
28	Regions Hospital	Saint Paul	Minnesota	United States	55101
29	Memorial Sloan Kettering Cancer Center	Basking Ridge	New Jersey	United States	07920
30	Memorial Sloan Kettering Cancer Center	Montvale	New Jersey	United States	07645
31	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
32	Memorial Sloan Kettering Cancer Center	Commack	New York	United States	11725
33	Memorial Sloan Kettering Cancer Center	Harrison	New York	United States	10604
34	Mount Sinai School of Medicine	New York	New York	United States	10029-6574
35	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
36	Stony Brook University Medical Center	Stony Brook	New York	United States	11794-9452
37	Memorial Sloan Kettering Cancer Center	Uniondale	New York	United States	11553
38	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
39	Precision Cancer Research -Dayton Physicians Network	Middletown	Ohio	United States	45042
40	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma	United States	73104
41	Earle A. Chiles Research Institute	Portland	Oregon	United States	97213
42	Oregon Health & Science University	Portland	Oregon	United States	97239
43	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
44	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
45	Cancer Treatment Centers of America, Philadelphia	Philadelphia	Pennsylvania	United States	19124
46	Rhode Island Hospital-Lifespan Cancer Institute	Providence	Rhode Island	United States	02903
47	Sanford Cancer Center	Sioux Falls	South Dakota	United States	57104
48	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
49	Inova Dwight and Martha Schar Cancer Institute	Fairfax	Virginia	United States	22031
50	MultiCare Regional Cancer Center - Gig Harbor	Auburn	Washington	United States	98801
51	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
52	Site AU61002	Douglas	Queensland	Australia	4814
53	Site AU61011	Tugun	Queensland	Australia	4224
54	Site AU61008	Adelaide	South Australia	Australia	5011
55	Site AU61006	East Bentleigh	Victoria	Australia	3165
56	Site AU61007	Kogarah		Australia	2217
57	Site BE32007	Edegem	Antwerpen	Belgium	2650
58	Site BE32001	Bruxelles	Bruxelles-Capitale, Région De	Belgium	1200
59	Site BE32008	Mons	Hainaut	Belgium	7000
60	Site BE32002	Bruxelles	Liege	Belgium	1050
61	Site BE32012	Gent	Oost-Vlaanderen	Belgium	9000
62	Site BE32006	Leuven	Vlaams Brabant	Belgium	3000
63	Site BE32005	Brugge		Belgium	8310
64	Site BE32004	Brussels		Belgium	1000
65	Site BE32011	Charleroi		Belgium	6000
66	Site BE32010	Haine-Saint-Paul		Belgium	7100
67	Site BR55010	Brasília	Distrito Federal	Brazil	70200-730
68	Site BR55006	Lajeado	Rio Grande Do Sul	Brazil	95900000
69	Site BR55002	Itajai	Santa Catarina	Brazil	88301-220
70	Site BR55003	Santo Andre	Sao Paulo	Brazil	09060-650
71	Site BR55005	Sao Jose do Rio Preto	Sao Paulo	Brazil	15090-000
72	Site BR55007	Barretos	São Paulo	Brazil	14784-400
73	Site BR55017	Belo Horizonte		Brazil	30130-090
74	Site BR55016	Passo Fundo		Brazil	99010-260
75	Site BR55015	Rio de Janeiro		Brazil	22793-080
76	Site BR55018	Santa Catarina		Brazil	88501-003
77	Site BR55009	São Paulo		Brazil	01509-900
78	Site BR55004	São Paulo		Brazil	08270-070
79	Site CA15005	Edmonton	Alberta	Canada	T6G 1Z2
80	Site CA15009	Saint-John	New Brunswick	Canada	E2L 4L4
81	Site CA15011	Toronto	Ontario	Canada	M5G 1X5
82	Site CA15002	Montreal	Quebec	Canada	H3T 1M5
83	Site CA15008	Montreal	Quebec	Canada	H4A 3J1
84	Site CL56003	Providencia	Santiago	Chile	7500921
85	Site CL56008	Providencia		Chile	7520378
86	Site CL56005	Santiago		Chile	8330032
87	Site CL56007	Valdivia		Chile	5090000
88	Site CN86003	Haerbin	Heilongjiang	China	150081
89	Site CN86006	Nanjing	Jiangsu	China	210008
90	Site CN86004	Hangzhou Shi	Zhejiang	China	310003
91	Site CN86009	Beijing		China	100030
92	Site CN86002	Beijing		China	100071
93	Site CN86005	Hefei		China	230022
94	Site CN86001	Xiamen		China
95	Site CN86008	Zhengzhou		China	450000
96	Site CO57006	Medellín	Antioquia	Colombia	574
97	Site CO57007	Monteria	Córdoba	Colombia	230002
98	Site CO57009	Bogota	DC	Colombia	110231
99	Site CO57005	Cali	Valle	Colombia
100	Site CO57001	Cali		Colombia
101	Site CO57002	Medellin		Colombia	0574
102	Site FR33009	Dijon	Bourgogne	France	21079
103	Site FR33010	Brest Cedex	Bretagne	France	29609
104	Site FR33001	Rennes	Bretagne	France	35042
105	Site FR33008	Besancon cedex	Franche-Comte	France	25033
106	Site FR33011	Montpellier Cedex 5	Languedoc-Roussillon	France	34298
107	Site FR33002	Paris cedex	Paris	France	75970
108	Site FR33101	St Herblain	Pays-de-la-Loire	France	44805
109	Site FR33005	Nice	Provence-Alpes-Côte-d'Azur	France	06200
110	Site FR33003	Lyon	Rhone	France	69008
111	Site FR33006	Poitiers	Vienne	France	86021
112	Site FR33103	Creteil		France	94000
113	Site FR33007	Nice Cedex 2		France	06189
114	Site FR33104	Saint Priest en Jarez		France	42270
115	Site DE49008	Munich	Bavaria	Germany	81377
116	Site DE49007	Munchen	Bayern	Germany	81925
117	Site DE49002	Mainz	Rheinland-Pfalz	Germany	55101
118	Site DE49021	Halle	Sachsen-Anhalt	Germany	06108
119	Site DE49015	Magdeburg	Sachsen-Anhalt	Germany	39104
120	Site DE49010	Dresden	Sachsen	Germany	01307
121	Site DE49004	Leipzig	Sachsen	Germany	04103
122	Site DE49012	Berlin		Germany	13125
123	Site DE49011	Berlin		Germany	13353
124	Site DE49018	Dresden		Germany	1067
125	Site DE49019	Heilbronn		Germany	74078
126	Site IL97206	Kfar Saba	HaMerkaz	Israel	44281
127	Site IL97210	HaDarom		Israel	7030000
128	Site IL97201	Haifa		Israel	3109601
129	Site IL97209	Holon		Israel	58100
130	Site IL97202	Jerusalem		Israel	91031
131	Site IL97203	Tel Aviv		Israel	64239
132	Site IT39011	Meldola	Forli	Italy	47014
133	Site IT39020	Monza	Lombardia	Italy	20052
134	Site IT39023	Vicenza	VI	Italy	36100
135	Site IT39013	Ancona		Italy	60126
136	Site IT39004	Bergamo		Italy	24127
137	Site IT39009	Cremona		Italy	26100
138	Site IT39006	Milano		Italy	20132
139	Site IT39008	Milano		Italy	20141
140	Site IT39021	Modena		Italy	41124
141	Site IT39016	Padova		Italy	35128
142	Site IT39012	Parma		Italy	43126
143	Site IT39018	Perugia		Italy	05100
144	Site IT39003	Piacenza		Italy	29100
145	Site IT39019	Pisa		Italy	56126
146	Site IT39022	Reggio Emilia		Italy	42123
147	Site IT39015	Roma		Italy	00128
148	Site IT39026	Terni		Italy	5100
149	Site IT39024	Turin TO		Italy	5-10126
150	Site JP81009	Nagoya	Aichi	Japan
151	Site JP81003	Kashiwa	Chiba	Japan
152	Site JP81002	Matsuyama	Ehime	Japan
153	Site JP81007	Sapporo	Hokkaido	Japan
154	Site JP81014	Kobe	Hyogo	Japan
155	Site JP81001	Suita	Osaka	Japan
156	Site JP81015	Hidaka	Saitama	Japan
157	Site JP81010	Kitaadachi-gun	Saitama	Japan
158	Site JP81012	Sunto-gun	Shizuoka	Japan
159	Site JP81013	Bunkyo-ku	Tokyo	Japan
160	Site JP81006	Chuo-ku	Tokyo	Japan
161	Site JP81008	Koto-ku	Tokyo	Japan
162	Site JP81005	Fukuoka		Japan
163	Site JP81004	Osaka		Japan
164	Site JP81011	Osaka		Japan
165	Site KR82002	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
166	Site KR82009	Suwon-si	Gyeonggido [Kyonggi-do]	Korea, Republic of	16247
167	Site KR82004	Seoul	Seoul Teugbyeolsi	Korea, Republic of	06351
168	Site KR82008	Incheon		Korea, Republic of	21556
169	Site KR82003	Seoul		Korea, Republic of	03080
170	Site KR82005	Seoul		Korea, Republic of	05505
171	Site KR82007	Seoul		Korea, Republic of	152-703
172	Site KR82006	Seoul		Korea, Republic of	6591
173	Site MX52007	Ciudad de México	Distrito Federal	Mexico	3100
174	Site MX52002	Mexico	Distrito Federal	Mexico	06760
175	Site MX52010	Veracruz, Ver	Veracruz	Mexico	91900
176	Site MX52001	Aguascalientes		Mexico	20230
177	Site MX52003	Distrito Federal		Mexico	06720
178	Site MX52009	Jalisco		Mexico	45030
179	Site MX52004	Oaxaca		Mexico
180	Site MX52008	San Luis De Potosi		Mexico	78250
181	Site PE51004	San Isidro	Lima	Peru	L27
182	Site PE51003	Arequipa		Peru	4001
183	Site PE51005	Lima		Peru	15036
184	Site PE51006	Lima		Peru	15072
185	Site PE51001	Lima		Peru	L27
186	Site PL48004	Lublin	Lubuskie	Poland	20-090
187	Site PL48007	Ostroleka	Mazowieckie	Poland	07-410
188	Site PL48005	Wieliszew	Mazowieckie	Poland	05-135
189	Site PL48002	Brzozow	Podkarpackie	Poland	36-20
190	Site PL48009	Warszawa		Poland	02-781
191	Site ES34013	Badalona	Barcelona	Spain	08028
192	Site ES34010	Avila	Castilla Y Leon	Spain	05004
193	Site ES34011	Alcorcon	Madrid	Spain	28925
194	Site ES34005	Barcelona		Spain	08003
195	Site ES34016	Barcelona		Spain	08025
196	Site ES34015	Barcelona		Spain	08035
197	Site ES34019	Burgos		Spain	09006
198	Site ES34008	Madrid		Spain	28007
199	Site ES34017	Madrid		Spain	28033
200	Site ES34004	Madrid		Spain	28034
201	Site ES34003	Murcia		Spain	30120
202	Site ES34018	Sevilla		Spain	41009
203	Site ES34006	Zaragoza		Spain	50009
204	Site TW88605	Kwei-Shan	Taoyuan	Taiwan	333
205	Site TW88608	Kaohsiung		Taiwan	80756
206	Site TW88604	Kaohsiung		Taiwan	833
207	Site TW88603	Taichung		Taiwan	404
208	Site TW88607	Tainan		Taiwan	704
209	Site TW88606	Taipei		Taiwan	10002
210	Site TW88601	Taipei		Taiwan	112
211	Site GB44003	Aberdeen	Aberdeenshire	United Kingdom	AB25 2ZN
212	Site GB44101	London	London, City Of	United Kingdom	SW3 6JJ
213	Site GB44102	Sutton	Surrey	United Kingdom	SM2 5PT
214	Site GB44103	Cambridge		United Kingdom	CB2 0QQ
215	Site GB44009	Coventry		United Kingdom	CV2 2DX
216	Site GB44104	Dundee		United Kingdom	DD2 4BF
217	Site GB44008	Leeds		United Kingdom	LS7 9TF
218	Site GB44002	London		United Kingdom	NW1 2PG
219	Site GB44004	London		United Kingdom	W1G 6AD
220	Site GB44001	Manchester		United Kingdom	M20 4BX