A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection. (COMBI-AD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01682083
First received: September 6, 2012
Last updated: August 13, 2015
Last verified: July 2015
  Purpose

This is 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 will be screened for eligibility. Subjects will be 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 Intervention Phase
Melanoma
Drug: Dabrafenib
Drug: Trametinib
Drug: Placebos
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Relapse-free survival (RFS) [ Time Frame: Approximately 32 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 32 months ] [ Designated as safety issue: No ]
  • Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 32 months ] [ Designated as safety issue: No ]
  • Safety of dabrafenib and trametinib as a combination therapy in the overall study population [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 852
Study Start Date: January 2013
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabrafenib and trametinib combination therapy
Subjects will receive dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months.
Drug: Dabrafenib
Each capsule contains 50 mg or 75 mg of free base (present as the mesylate salt)
Drug: Trametinib
Each tablet contains 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)
Placebo Comparator: Dabrafenib and trametinib placebos
Subjects will receive matching placebos orally for 12 months
Drug: Placebos
The placebo capsules and tablets contain the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01682083

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Locations
United States, Alabama
GSK Investigational Site
Birmingham, Alabama, United States, 35243
United States, Arizona
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Tucson, Arizona, United States, 85724-5024
United States, California
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San Francisco, California, United States, 94115
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San Francisco, California, United States, 94143
United States, Colorado
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Aurora, Colorado, United States, 80045
United States, Connecticut
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Farmington, Connecticut, United States, 06030
United States, Florida
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Fort Myers, Florida, United States, 33916
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Lake Worth, Florida, United States, 33461
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Orlando, Florida, United States, 32806
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St. Petersburg, Florida, United States, 33705
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Stuart, Florida, United States, 34994
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Tampa, Florida, United States, 33612
United States, Georgia
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Atlanta, Georgia, United States, 30322
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Atlanta, Georgia, United States, 30341
United States, Indiana
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Indianapolis, Indiana, United States, 46202
United States, Maryland
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Baltimore, Maryland, United States, 21237
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Lutherville Timonium, Maryland, United States, 21093
United States, Massachusetts
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Boston, Massachusetts, United States, 02114
United States, Michigan
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Ann Arbor, Michigan, United States, 48019
United States, New Jersey
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Morristown, New Jersey, United States, 07960
United States, North Carolina
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Winston-Salem, North Carolina, United States, 27157
United States, Ohio
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Cincinnati, Ohio, United States, 45242
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Columbus, Ohio, United States, 43210
United States, Oregon
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Portland, Oregon, United States, 97213
United States, Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
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Nashville, Tennessee, United States, 37203
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Nashville, Tennessee, United States, 37232-5536
United States, Texas
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Dallas, Texas, United States, 75230
United States, Utah
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Murray, Utah, United States, 84107
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Seattle, Washington, United States, 98109
Argentina
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Capital Federal, Buenos Aires, Argentina, C1426ANZ
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Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1050AAK
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Viedma, Río Negro, Argentina, R8500ACE
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Rosario, Santa Fe, Argentina, S2000KZE
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Ciudad Autónoma de Buenos Aires, Argentina, C1121ABE
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Santa Fe, Argentina, 3000
Australia, New South Wales
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Gateshead, New South Wales, Australia, 2290
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North Sydney, New South Wales, Australia, 2060
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Tweed Heads, New South Wales, Australia, 2485
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Westmead, New South Wales, Australia, 2145
Australia, Queensland
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Greenslopes, Queensland, Australia, 4120
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Milton, Queensland, Australia, 4064
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Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
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Adelaide, South Australia, Australia, 5000
Australia, Victoria
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Box Hill, Victoria, Australia, 3128
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Heidelberg, Victoria, Australia, 3084
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Melbourne, Victoria, Australia, 3004
Australia, Western Australia
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Nedlands, Western Australia, Australia, 6009
Austria
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Graz, Austria, 8036
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Innsbruck, Austria, 6020
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Linz, Austria, A-4010
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Salzburg, Austria, A-5020
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Wels, Austria, A-4600
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Wien, Austria, 1090
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Wien, Austria, A-1030
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Wien, Austria, A-1220
Belgium
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Brussels, Belgium, 1200
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Leuven, Belgium, 3000
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Liège, Belgium, 4000
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Wilrijk, Belgium, 2610
Brazil
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Goiânia, Goiás, Brazil, 74605-030
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Curitiba, Paraná, Brazil, 81520-060
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RJ, Rio De Janeiro, Brazil, 22 260-020
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Ijui, Rio Grande Do Sul, Brazil, 98700-000
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São Paulo - SP, Brazil, 01323-900
Canada, Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
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Hamilton, Ontario, Canada, L8V 5C2
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Oshawa, Ontario, Canada, L1G 2B9
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Ottawa, Ontario, Canada, K1H 8L6
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Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
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Montreal, Quebec, Canada, H2W 1S6
Canada
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Quebec, Canada, G1R 2J6
Czech Republic
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Brno, Czech Republic, 656 53
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Hradec Kralove, Czech Republic, 500 05
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Olomouc, Czech Republic, 775 20
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Praha 10, Czech Republic, 100 34
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Praha 2, Czech Republic, 128 08
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Zlin, Czech Republic, 76275
Denmark
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Herlev, Denmark, 2730
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Odense, Denmark, 5000 C
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Århus C, Denmark, 8000
France
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Bordeaux, France, 33075
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Boulogne-Billancourt, France, 92100
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Brest cedex, France, 29609
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Dijon, France, 21079
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Grenoble, France, 38043
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Lille, France, 59037
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Marseille cedex 5, France, 13385
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Montpellier cedex 5, France, 34295
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Nice, France, 06202
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Paris, France, 75006
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Paris Cedex 10, France, 75475
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Pierre-Bénite cedex, France, 69495
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Reims Cedex, France, 51092
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Rennes Cedex, France, 35042
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Toulouse cedex 9, France, 31059
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Tours Cedex 9, France, 37044
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Villejuif cedex, France, 94805
Germany
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Freiburg, Baden-Wuerttemberg, Germany, 79104
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Heidelberg, Baden-Wuerttemberg, Germany, 69120
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Heilbronn, Baden-Wuerttemberg, Germany, 74078
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Mannheim, Baden-Wuerttemberg, Germany, 68167
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Tuebingen, Baden-Wuerttemberg, Germany, 72076
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Ulm, Baden-Wuerttemberg, Germany, 89081
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Muenchen, Bayern, Germany, 80804
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Muenchen, Bayern, Germany, 80337
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Nuernberg, Bayern, Germany, 90419
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Regensburg, Bayern, Germany, 93053
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Wuerzburg, Bayern, Germany, 97080
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Darmstadt, Hessen, Germany, 64297
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Kassel, Hessen, Germany, 34125
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Marburg, Hessen, Germany, 35043
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Wiesbaden, Hessen, Germany, 65199
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Schwerin, Mecklenburg-Vorpommern, Germany, 19049
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Buxtehude, Niedersachsen, Germany, 21614
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Hannover, Niedersachsen, Germany, 30625
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Aachen, Nordrhein-Westfalen, Germany, 52074
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Bochum, Nordrhein-Westfalen, Germany, 44791
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Bonn, Nordrhein-Westfalen, Germany, 53127
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Essen, Nordrhein-Westfalen, Germany, 45122
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Koeln, Nordrhein-Westfalen, Germany, 50937
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Muenster, Nordrhein-Westfalen, Germany, 48149
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Mainz, Rheinland-Pfalz, Germany, 55131
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Homburg, Saarland, Germany, 66421
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Magdeburg, Sachsen-Anhalt, Germany, 39120
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Quedlinburg, Sachsen-Anhalt, Germany, 06484
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Kiel, Schleswig-Holstein, Germany, 24105
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Luebeck, Schleswig-Holstein, Germany, 23538
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Erfurt, Thueringen, Germany, 99089
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Gera, Thueringen, Germany, 07548
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Berlin, Germany, 10249
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Berlin, Germany, 13585
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Berlin, Germany, 10117
Greece
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Athens, Greece, 11527
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Thessaloniki, Greece, 564 29
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Thessaloniki, Greece, 54622
Israel
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Jerusalem, Israel, 91120
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Ramat Gan, Israel, 52621
Italy
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Roma, Lazio, Italy, 00167
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Genova, Liguria, Italy, 16132
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Bergamo, Lombardia, Italy, 24127
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Milano, Lombardia, Italy, 20141
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Milano, Lombardia, Italy, 20133
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Candiolo, Piemonte, Italy, 10060
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Pisa, Toscana, Italy, 56126
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Padova, Veneto, Italy, 35128
Japan
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Shizuoka, Japan, 411-8777
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Tokyo, Japan, 104-0045
Netherlands
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Amsterdam, Netherlands, 1081 HV
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Amsterdam, Netherlands, 1066 CX
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Groningen, Netherlands, 9713 GZ
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Leeuwarden, Netherlands, 8934 AD
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Maastricht, Netherlands, 6229 HX
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Nijmegen, Netherlands, 6525 GA
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Rotterdam, Netherlands, 3075 EA
New Zealand
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Auckland, New Zealand, 0622
Norway
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Oslo, Norway, 0310
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Ålesund, Norway, 6026
Poland
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Gdansk, Poland, 80-215
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Konin, Poland, 62-500
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Poznan, Poland, 60-693
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Warszawa, Poland, 02-781
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Warszawa, Poland, 04-125
Russian Federation
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Chelyabinsk, Russian Federation, 454087
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Moscow, Russian Federation, 115478
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Moscow, Russian Federation, 143423
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Ryazan, Russian Federation, 390011
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St. Petersburg, Russian Federation
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St. Petersburg, Russian Federation, 197758
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St. Petersburg, Russian Federation, 191104
GSK Investigational Site
Volzhsky, Russian Federation, 404130
Spain
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Badalona, Spain, 08916
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Barcelona, Spain, 08036
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Barcelona, Spain, 08035
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Cartagena (Murcia), Spain, 30202
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Las Palmas De Gran Canaria, Spain, 35016
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Madrid, Spain, 28034
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Madrid, Spain, 28041
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Madrid, Spain, 28046
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Málaga, Spain, 29010
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Palma de Mallorca, Spain, 07198
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Pamplona, Spain, 31008
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San Sebastián, Spain, 20014
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Santander, Spain, 39008
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Sevilla, Spain, 41014
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Valencia, Spain, 46014
Sweden
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Göteborg, Sweden, SE-413 45
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Lund, Sweden, SE-221 85
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Stockholm, Sweden, SE-171 76
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Uppsala, Sweden, SE-751 85
Switzerland
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Basel, Switzerland, 4031
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Chur, Switzerland, 7000
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Zürich, Switzerland, 8091
Taiwan
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Taichung, Taiwan, 404
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Taipei, Taiwan, 100
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Taoyuan, Taiwan, 333
United Kingdom
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Northwood, Middlesex, United Kingdom, HA6 2RN
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Exeter, United Kingdom, EX2 5DW
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Glasgow, United Kingdom, G12 0YN
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Guildford, United Kingdom, GU2 7XX
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Leeds, United Kingdom, LS9 7TF
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London, United Kingdom, NW3 2QG
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London, United Kingdom, SW3 6JJ
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London, United Kingdom, W1G 6AD
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Manchester, United Kingdom, M20 4BX
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Newcastle upon Tyne, United Kingdom, NE7 7DN
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Norwich, United Kingdom, NR4 7UY
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Preston, United Kingdom, PR2 9HT
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Southampton, United Kingdom, SO16 6YD
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Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01682083     History of Changes
Other Study ID Numbers: 115532
Study First Received: September 6, 2012
Last Updated: August 13, 2015
Health Authority: United States: Food and Drug Administration
Australia: Human Research Ethics Committee

Keywords provided by GlaxoSmithKline:
trametinib
adjuvant melanoma
dabrafenib
BRAF inhibitor
MEK inhibitor
BRAF mutation-positive melanoma
dabrafenib and trametinib combination therapy
Oncology

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Dabrafenib
Trametinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 30, 2015