Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD).

COMBI-AD: A Phase III Randomized Double Blind Study of Dabrafenib (GSK2118436) in COMBInation With Trametinib (GSK1120212) Versus Two Placebos in the ADjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection

ClinicalTrials.gov Identifier: NCT01682083

Novartis Reference Number: 115532

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

This was a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma were screened for eligibility. Subjects were randomized to receive either dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD]) combination therapy or two placebos for 12 months.

Condition 
Melanoma
Phase 
Phase 3
Overall status 
Active, not recruiting
Enrollment count 
870 participants
Start date 
Jan 08, 2013
Completion date 
Dec 30, 2022
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Dabrafenib
Each capsule contained 50 mg or 75 mg of free base (present as the mesylate salt)
Drug
Trametinib
Each tablet contained 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)
Drug
Placebos
The placebo capsules and tablets contained the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment

Eligibility Criteria

Key Inclusion Criteria:

Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
Surgically rendered free of disease no more than 12 weeks before randomization.
Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
Adequate hematologic, hepatic, renal and cardiac function.

Key Exclusion Criteria:

Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases.
Evidence of distant metastatic disease.
Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for melanoma is allowed.
History of another malignancy or concurrent malignancy including prior malignant melanoma. Exceptions to this include: Patients who have been disease-free for 5 years or patients with a history completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, or other malignancies for which the patient has been disease free for > 5 years.
History or current evidence of cardiovascular risk.
History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Study Locations

United States
Novartis Investigative Site
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Birmingham, 35243
Alabama
United States
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Tucson, 85719
Arizona
United States
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San Francisco, 94115
California
United States
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San Francisco, 94143
California
United States
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Aurora, 80045
Colorado
United States
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Farmington, 06030
Connecticut
United States
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Fort Myers, 33916
Florida
United States
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Lake Worth, 33461
Florida
United States
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Orlando, 32806
Florida
United States
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Saint Petersburg, 33705
Florida
United States
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Stuart, 34994
Florida
United States
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Tampa, 33612
Florida
United States
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Atlanta, 30322
Georgia
United States
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Atlanta, 30341
Georgia
United States
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Indianapolis, 46202
Indiana
United States
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Baltimore, 21237
Maryland
United States
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Lutherville-Timonium, 21093
Maryland
United States
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Boston, 02114
Massachusetts
United States
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Ann Arbor, 48019
Michigan
United States
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Morristown, 07960
New Jersey
United States
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Winston-Salem, 27157
North Carolina
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Cincinnati, 45242
Ohio
United States
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Columbus, 43210
Ohio
United States
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Portland, 97213
Oregon
United States
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Pittsburgh, 15232
Pennsylvania
United States
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Nashville, 37203
Tennessee
United States
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Nashville, 37232-5536
Tennessee
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Dallas, 75230
Texas
United States
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Murray, 84107
Utah
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Seattle, 98109
Washington
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Argentina
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Capital Federal, C1426ANZ
Buenos Aires
Argentina
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Ciudad Autonoma de Buenos Aires, C1050AAK
Buenos Aires
Argentina
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Viedma, R8500ACE
Río Negro
Argentina
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Rosario, S2000KZE
Santa Fe
Argentina
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Ciudad Autonoma de Buenos Aires, C1025ABH
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Argentina
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Ciudad Autonoma de Buenos Aires, C1121ABE
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Argentina
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Santa Fe, 3000
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Argentina
Australia
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Gateshead, 2290
New South Wales
Australia
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North Sydney, 2060
New South Wales
Australia
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Tweed Heads, 2485
New South Wales
Australia
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Westmead, 2145
New South Wales
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Greenslopes, 4120
Queensland
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Milton, 4064
Queensland
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Woolloongabba, 4102
Queensland
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Adelaide, 5000
South Australia
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Box Hill, 3128
Victoria
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Heidelberg, 3084
Victoria
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Melbourne, 3004
Victoria
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Nedlands, 6009
Western Australia
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Austria
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Graz, 8036
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Austria
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Innsbruck, 6020
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Linz, A-4010
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Salzburg, A-5020
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Wels, A-4600
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Wien, 1090
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Wien, A-1030
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Wien, A-1220
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Brussels, 1200
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Leuven, 3000
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Liege, 4000
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Wilrijk, 2610
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Goiania, 74605-030
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Curitiba, 81520-060
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Ijui, 98700-000
Rio Grande Do Sul
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Rio De Janeiro, 22 260-020
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Brazil
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São Paulo, 01323-900
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Edmonton, T6G 1Z2
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Toronto, M5G 2M9
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Montreal, H2W 1S6
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Brno, 656 53
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Hradec Kralove, 500 05
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Olomouc, 775 20
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Praha 2, 128 08
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Arhus C, 8000
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Herlev, 2730
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Denmark
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Odense, 5000 C
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Denmark
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Bordeaux, 33075
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Dijon, 21079
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Grenoble, 38043
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Lille, 59037
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Marseille cedex 5, 13385
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Montpellier cedex 5, 34295
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Nice, 06202
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Paris Cedex 10, 75475
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Paris, 75006
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Pierre-Benite cedex, 69495
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France
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Reims Cedex, 51092
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France
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Rennes Cedex, 35042
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Toulouse cedex 9, 31059
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Tours Cedex 9, 37044
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Heilbronn, 74078
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Mannheim, 68167
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Tuebingen, 72076
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Ulm, 89081
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Muenchen, 80337
Bayern
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Muenchen, 80804
Bayern
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Nuernberg, 90419
Bayern
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Regensburg, 93053
Bayern
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Wuerzburg, 97080
Bayern
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Darmstadt, 64297
Hessen
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Kassel, 34125
Hessen
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Marburg, 35043
Hessen
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Wiesbaden, 65199
Hessen
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Schwerin, 19049
Mecklenburg-Vorpommern
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Buxtehude, 21614
Niedersachsen
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Hannover, 30625
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Aachen, 52074
Nordrhein-Westfalen
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Bochum, 44791
Nordrhein-Westfalen
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Bonn, 53127
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Essen, 45122
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Koeln, 50937
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Muenster, 48149
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Mainz, 55131
Rheinland-Pfalz
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Homburg, 66421
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Magdeburg, 39120
Sachsen-Anhalt
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Quedlinburg, 06484
Sachsen-Anhalt
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Kiel, 24105
Schleswig-Holstein
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Luebeck, 23538
Schleswig-Holstein
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Erfurt, 99089
Thueringen
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Gera, 07548
Thueringen
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Berlin, 10117
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Germany
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Berlin, 10249
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Germany
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Berlin, 13585
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Germany
Greece
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Athens, 11527
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Greece
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Thessaloniki, 54622
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Greece
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Thessaloniki, 564 29
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Greece
Israel
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Jerusalem, 91120
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Israel
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Ramat Gan, 52621
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Israel
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Roma, 00167
Lazio
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Genova, 16132
Liguria
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Bergamo, 24127
Lombardia
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Milano, 20133
Lombardia
Italy
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Milano, 20141
Lombardia
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Candiolo, 10060
Piemonte
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Pisa, 56126
Toscana
Italy
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Padova, 35128
Veneto
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Japan
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Shizuoka, 411-8777
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Japan
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Tokyo, 104-0045
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Japan
Netherlands
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Amsterdam, 1066 CX
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Amsterdam, 1081 HV
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Groningen, 9713 GZ
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Leeuwarden, 8934 AD
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Netherlands
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Maastricht, 6229 HX
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Nijmegen, 6525 GA
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Rotterdam, 3015 GD
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New Zealand
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Auckland, 0622
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New Zealand
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Alesund, 6026
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Oslo, 0310
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Gdansk, 80-215
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Konin, 62-500
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Poznan, 60-693
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Warszawa, 02-781
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Warszawa, 04-125
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Chelyabinsk, 454087
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Moscow, 115478
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Moscow, 143423
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Ryazan, 390011
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St. Petersburg, 197758
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Russian Federation
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St. Petersburg,
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Barcelona, 08036
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Madrid, 28041
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Spain
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Madrid, 28046
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Malaga, 29010
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Palma de Mallorca, 07198
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