- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01245062
GSK1120212 vs Chemotherapy in Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma
A Phase III Randomized, Open-label Study Comparing GSK1120212 to Chemotherapy in Subjects With Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Ciudad Autonoma de Buenos Aires, Argentina, C1121ABE
- GSK Investigational Site
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Australian Capital Territory
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Garran, Australian Capital Territory, Australia, 2606
- GSK Investigational Site
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New South Wales
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Port Macquarie, New South Wales, Australia, 2444
- GSK Investigational Site
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Waratah, New South Wales, Australia, 2300
- GSK Investigational Site
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Queensland
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South Brisbane, Queensland, Australia, 4101
- GSK Investigational Site
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Townsville, Queensland, Australia, 4810
- GSK Investigational Site
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Woolloongabba, Queensland, Australia, 4102
- GSK Investigational Site
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South Australia
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Kurralta Park, South Australia, Australia, 5037
- GSK Investigational Site
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Woodville, South Australia, Australia, 5011
- GSK Investigational Site
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Victoria
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Heidelberg, Victoria, Australia, 3084
- GSK Investigational Site
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Melbourne, Victoria, Australia, 3004
- GSK Investigational Site
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Graz, Austria, 8036
- GSK Investigational Site
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Wien, Austria, 1090
- GSK Investigational Site
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Brussels, Belgium, 1200
- GSK Investigational Site
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Charleroi, Belgium, 6000
- GSK Investigational Site
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Gent, Belgium, 9000
- GSK Investigational Site
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Jette, Belgium, 1090
- GSK Investigational Site
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Kortrijk, Belgium, 8500
- GSK Investigational Site
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Leuven, Belgium, 3000
- GSK Investigational Site
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Wilrijk, Belgium, 2610
- GSK Investigational Site
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Yvoir, Belgium, 5530
- GSK Investigational Site
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Alberta
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Calgary, Alberta, Canada, T2N 4N2
- GSK Investigational Site
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E6
- GSK Investigational Site
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 2Y9
- GSK Investigational Site
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Ontario
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Hamilton, Ontario, Canada, L8V 5C2
- GSK Investigational Site
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London, Ontario, Canada, N6A 4L6
- GSK Investigational Site
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Oshawa, Ontario, Canada, L1G 2B9
- GSK Investigational Site
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Ottawa, Ontario, Canada, K1H 8L6
- GSK Investigational Site
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Toronto, Ontario, Canada, M5G 2M9
- GSK Investigational Site
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Quebec
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Montreal, Quebec, Canada, H2L 4M1
- GSK Investigational Site
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Montreal, Quebec, Canada, H2W 1S6
- GSK Investigational Site
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Hradec Kralove, Czechia, 500 05
- GSK Investigational Site
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Ostrava, Czechia, 708 52
- GSK Investigational Site
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Praha 2, Czechia, 128 08
- GSK Investigational Site
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Zlin, Czechia, 76275
- GSK Investigational Site
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Boulogne-Billancourt, France, 92100
- GSK Investigational Site
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Grenoble, France, 38043
- GSK Investigational Site
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Montpellier, France, 34295
- GSK Investigational Site
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Nantes, France, 44093
- GSK Investigational Site
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Paris Cedex 10, France, 75475
- GSK Investigational Site
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Pierre-Benite cedex, France, 69495
- GSK Investigational Site
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Rennes, France, 35042
- GSK Investigational Site
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Tours, France, 37044
- GSK Investigational Site
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Villejuif, France, 94805
- GSK Investigational Site
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Berlin, Germany, 10117
- GSK Investigational Site
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Baden-Wuerttemberg
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Heidelberg, Baden-Wuerttemberg, Germany, 69120
- GSK Investigational Site
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Mannheim, Baden-Wuerttemberg, Germany, 68167
- GSK Investigational Site
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Tuebingen, Baden-Wuerttemberg, Germany, 72076
- GSK Investigational Site
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Bayern
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Muenchen, Bayern, Germany, 80804
- GSK Investigational Site
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Wuerzburg, Bayern, Germany, 97080
- GSK Investigational Site
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Niedersachsen
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Buxtehude, Niedersachsen, Germany, 21614
- GSK Investigational Site
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Nordrhein-Westfalen
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Essen, Nordrhein-Westfalen, Germany, 45122
- GSK Investigational Site
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Sachsen
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Dresden, Sachsen, Germany, 01307
- GSK Investigational Site
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Schleswig-Holstein
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Luebeck, Schleswig-Holstein, Germany, 23538
- GSK Investigational Site
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Athens, Greece, 11527
- GSK Investigational Site
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Athens, Greece, 185 47
- GSK Investigational Site
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Thessaloniki, Greece, 564 29
- GSK Investigational Site
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Lombardia
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Milano, Lombardia, Italy, 20132
- GSK Investigational Site
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Milano, Lombardia, Italy, 20133
- GSK Investigational Site
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Milano, Lombardia, Italy, 20141
- GSK Investigational Site
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Toscana
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Pisa, Toscana, Italy, 56126
- GSK Investigational Site
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Christchurch, New Zealand, 8011
- GSK Investigational Site
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Dunedin, New Zealand, 9016
- GSK Investigational Site
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Newtown, Wellington, New Zealand, 6002
- GSK Investigational Site
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Oslo, Norway, 0310
- GSK Investigational Site
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Poznan, Poland, 61-866
- GSK Investigational Site
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Warszawa, Poland, 02-781
- GSK Investigational Site
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Warszawa, Poland, 04-125
- GSK Investigational Site
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Chelyabinsk, Russian Federation, 454087
- GSK Investigational Site
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Magnitogorsk, Russian Federation, 455001
- GSK Investigational Site
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Moscow, Russian Federation, 115478
- GSK Investigational Site
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St. Petersburg, Russian Federation, 197758
- GSK Investigational Site
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Goteborg, Sweden, SE-413 45
- GSK Investigational Site
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Linkoping, Sweden, SE-581 85
- GSK Investigational Site
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Lund, Sweden, SE-221 85
- GSK Investigational Site
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Stockholm, Sweden, SE-171 76
- GSK Investigational Site
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Uppsala, Sweden, SE-751 85
- GSK Investigational Site
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Zurich, Switzerland, 8091
- GSK Investigational Site
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Dnepropetrovsk, Ukraine, 49102
- GSK Investigational Site
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Kharkiv, Ukraine, 61070
- GSK Investigational Site
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Kyiv, Ukraine, 03022
- GSK Investigational Site
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Kyiv, Ukraine, 03115
- GSK Investigational Site
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Lviv, Ukraine, 79031
- GSK Investigational Site
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Sumy, Ukraine, 40005
- GSK Investigational Site
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Sympheropol, Ukraine, 95023
- GSK Investigational Site
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Ternopil, Ukraine, 46023
- GSK Investigational Site
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Uzhgorod, Ukraine, 88017
- GSK Investigational Site
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Aberdeen, United Kingdom, AB25 2ZN
- GSK Investigational Site
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Birmingham, United Kingdom, B15 2TH
- GSK Investigational Site
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Chelmsford, United Kingdom, CM1 7ET
- GSK Investigational Site
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Leeds, United Kingdom, LS9 7TF
- GSK Investigational Site
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London, United Kingdom, SW3 6JJ
- GSK Investigational Site
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London, United Kingdom, W1G 6AD
- GSK Investigational Site
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Manchester, United Kingdom, M20 4BX
- GSK Investigational Site
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Oxford, United Kingdom, OX3 7LJ
- GSK Investigational Site
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Southampton, United Kingdom, SO16 6YD
- GSK Investigational Site
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Cambridgeshire
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Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
- GSK Investigational Site
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Middlesex
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Northwood, Middlesex, United Kingdom, HA6 2RN
- GSK Investigational Site
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Surrey
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Sutton, Surrey, United Kingdom, SM2 5PT
- GSK Investigational Site
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Arizona
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Tucson, Arizona, United States, 85724-5024
- GSK Investigational Site
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Florida
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Fort Myers, Florida, United States, 33916
- GSK Investigational Site
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Georgia
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Athens, Georgia, United States, 30607
- GSK Investigational Site
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Marietta, Georgia, United States, 30060
- GSK Investigational Site
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Iowa
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Iowa City, Iowa, United States, 52242
- GSK Investigational Site
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Louisiana
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Metairie, Louisiana, United States, 70006
- GSK Investigational Site
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Massachusetts
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Boston, Massachusetts, United States, 02114
- GSK Investigational Site
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New Jersey
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Morristown, New Jersey, United States, 07962-1956
- GSK Investigational Site
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Ohio
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Columbus, Ohio, United States, 43210
- GSK Investigational Site
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South Carolina
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Columbia, South Carolina, United States, 29210
- GSK Investigational Site
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Tennessee
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Chattanooga, Tennessee, United States, 37404
- GSK Investigational Site
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Memphis, Tennessee, United States, 38120
- GSK Investigational Site
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Nashville, Tennessee, United States, 37203
- GSK Investigational Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ≥18 years of age
- Stage III unresectable (Stage IIIc) or metastatic (Stage IV) cutaneous melanoma which is also determined to be BRAF V600E/K mutation-positive by the central laboratory
- Received no prior treatment or up to one prior regimen of chemotherapy for advanced or metastatic melanoma. Prior treatment with immunotherapy (with the exception of prior ipilimumab, which is only allowed if given in the adjuvant setting), cytokine therapy, biological or vaccine regimen is permitted. Prior use of sorafenib is allowed
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- Women of childbearing potential and men with reproductive potential must agree to use effective contraception during the study. Additionally women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- Adequate screening organ function
Exclusion Criteria:
- Any prior use of BRAF inhibitors or MEK inhibitors.
- Subjects who have received dacarbazine or paclitaxel prior to randomization will not be eligible to receive the same chemotherapy as study medication (i.e. a subject who received prior dacarbazine cannot receive dacarbazine on this trial and would thus receive paclitaxel if randomized to the control arm)
- History of another malignancy. Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor if unsure whether second malignancies meet requirements specified above
- Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed)
- Brain metastases with the following exceptions that are ALL confirmed by the GSK Medical Monitor:
All known lesions must be previously treated with surgery or stereotactic radiosurgery, and Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size) for ≥90 days prior to randomization (must be documented with two consecutive MRI or CT scans using contrast), and asymptomatic with no corticosteroids requirement for ≥ 30 days prior to randomization, and no enzyme-inducing anticonvulsants for ≥ 30 days prior to randomization
History or evidence of cardiovascular risk including any of the following:
- QTcB ≥ 480 msec.
- History or evidence of current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for >30 days prior to randomization are eligible
- History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization.
- History or evidence of current ≥ Class II congestive heart failure as defined by New York Heart Association
- History of interstitial lung disease or pneumonitis
History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):
- History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).
- Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
- Evidence of new optic disc cupping.
- Intraocular pressure > 21 mm Hg as measured by tonography
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: GSK1120212
MEK inhibitor
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MEK inhibitor
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Active Comparator: Chemotherapy
Investigator Choice of DTIC or paclitaxel
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Investigator Choice of DTIC or paclitaxel
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Experimental: Crossover
MEK inhibitor after documented progression on Chemotherapy Arm
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MEK inhibitor
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression-free Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases as Assessed by the Investigator and Independent Review
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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Progression-free survival (PFS) is defined as the time from randomization to the first documented occurrence of disease progression (PD) or death.
PFS for investigator-assessed and blinded, independent, central review committee (BRIC)-assessed responses was summarized per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, which is a set of published rules defining when cancer participants improve (respond), stay the same (stabilize), or worsen (progress) during treatment.
Disease progression is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
Primary Efficacy Population included all participants with BRAF V600E mutation-positive melanoma without a history of brain metastases.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression-free Survival in All Participants
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death.
Investigator-assessed and BRIC-assessed PFS were summarized per RECIST, Version 1.1.
PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
Intend-To-Treat (ITT) Population included all randomized participants regardless of whether or not treatment was administered.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and Without Prior Chemotherapy as Assessed by the Investigator
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death.
Investigator-assessed PFS was summarized per RECIST, Version 1.1.
PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and With Prior Chemotherapy as Assessed by the Investigator
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death.
Investigator-assessed PFS was summarized per RECIST, Version 1.1.
PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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Overall Survival in All Participants
Time Frame: Day 1 until death due to any cause (average of 20.3 months)
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Overall survival was defined as the time from the date of randomization to the date of death due to any cause.
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Day 1 until death due to any cause (average of 20.3 months)
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Overall Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases
Time Frame: Day 1 until death due to any cause (average of 20.3 months)
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Overall survival was defined as the time from the date of randomization to the date of death due to any cause.
NA indicates data was not available.
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Day 1 until death due to any cause (average of 20.3 months)
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Number of BRAF V600E Mutation-positive Participants Without a History of Brain Metastases With Overall Response (OR) as Assessed by the Investigator and Independent Review
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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OR is defined as the number of participants with evidence of complete response (CR; disappearance of all target lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator and an independent review per RECIST, Version 1.1.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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Number of Participants With OR as Assessed by the Investigator and Independent Review
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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OR is defined as the number of participants with evidence of complete response (disappearance of all target lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or partial response (at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator and an independent review per RECIST, Version 1.1.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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Number of BRAF V600E Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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OR is defined as the number of participants with evidence of complete response (disappearance of all extranodal lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or partial response (at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator per RECIST, Version 1.1.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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Number of BRAF V600K Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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OR is defined as the number of participants with evidence of complete response (CR; disappearance of all extranodal lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator per RECIST, Version 1.1.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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Number of Participants With OR Following Cross-over to Trametinib
Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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OR is defined as the number of participants with evidence of CR (disappearance of all target lesions.
Any pathological lymph node must be less than 10 millimeters in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator in participants following cross-over to Trametinib.
The evaluation was carried out by the Investigator per RECIST, Version 1.1.
Cross-over Population included the subset of participants who were randomized to CT and who elected to cross-over to Trametinib following disease progression on CT.
Only participants who received at least one dose of Trametinib were included in this population.
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Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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Duration of Response (DoR) for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classified as Confirmed Responders (CR or PR) as Assessed by the Investigator Review
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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DoR is defined as the time from the first documented evidence of CR (disappearance of all target lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until PD (at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation) or death due to any cause.
DoR for the investigator-assessed (INVA) response data were summarized per RECIST, Version 1.1.
Only those participants with confirmed response (CR and PR) were analyzed.
Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
NA indicates data was not available.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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DoR for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classified as Confirmed Responders (CR or PR) as Assessed by the Independent Review
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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DoR is defined as the time from the first documented evidence of CR (disappearance of all target lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until PD (at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation) or death due to any cause.
DoR for the independently-assessed (INDA) response data were summarized per RECIST, Version 1.1.
Only those participants with confirmed response (CR and PR) were analyzed.
Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
NA indicates data was not available.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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DoR for All Confirmed Responders (CR or PR) as Assessed by the Investigator Review
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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DoR is defined as the time from the first documented evidence of CR (disappearance of all target lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until PD or death due to any cause.
PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
DoR for the INVA response data was summarized per RECIST, Version 1.1.
Only those participants with confirmed response (CR and PR) were analyzed.
Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
NA indicates data was not available.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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DoR for All Confirmed Responders (CR or PR) as Assessed by the Independent Review
Time Frame: Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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DoR is defined as the time from the first documented evidence of CR (disappearance of all target lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until PD or death due to any cause.
PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
DoR for the INDA response data was summarized per RECIST, Version 1.1.
Only those participants with confirmed response (CR and PR) were analyzed.
Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
NA indicates data was not available.
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Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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DoR for All Responders (CR or PR) Following Cross-over to Trametinib as Assessed by the Investigator
Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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DoR is defined as the time from the first documented evidence of CR (disappearance of all extra nodal lesions.
Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until PD or death due to any cause.
PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
DoR data were summarized per RECIST, Version 1.1Only those participants with confirmed response (CR and PR) were analyzed.
Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
NA indicates data was not available.
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Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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PFS Following Cross-over to Trametinib as Assessed by the Investigator
Time Frame: Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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PFS is defined as the time from the first dose of cross-over therapy to the first documented occurrence of PD or death.
PFS was summarized per RECIST, Version 1.1.
PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
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Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Santiago-Walker A, Gagnon R, Mazumdar J, Casey M, Long GV, Schadendorf D, Flaherty K, Kefford R, Hauschild A, Hwu P, Haney P, O'Hagan A, Carver J, Goodman V, Legos J, Martin AM. Correlation of BRAF Mutation Status in Circulating-Free DNA and Tumor and Association with Clinical Outcome across Four BRAFi and MEKi Clinical Trials. Clin Cancer Res. 2016 Feb 1;22(3):567-74. doi: 10.1158/1078-0432.CCR-15-0321. Epub 2015 Oct 7.
- Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, Demidov LV, Hassel JC, Rutkowski P, Mohr P, Dummer R, Trefzer U, Larkin JM, Utikal J, Dreno B, Nyakas M, Middleton MR, Becker JC, Casey M, Sherman LJ, Wu FS, Ouellet D, Martin AM, Patel K, Schadendorf D; METRIC Study Group. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012 Jul 12;367(2):107-14. doi: 10.1056/NEJMoa1203421. Epub 2012 Jun 4.
- Robert C, Flaherty K, Nathan P, Hersey P, Garbe C, Milhem M, Demidov L, Mohr P, Hassel JC, Rutkowski P, Dummer R, Utikal J, Kiecker F, Larkin J, D'Amelio A Jr, Mookerjee B, Schadendorf D. Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K-mutant advanced or metastatic melanoma. Eur J Cancer. 2019 Mar;109:61-69. doi: 10.1016/j.ejca.2018.12.015. Epub 2019 Jan 25.
- Latimer NR, Bell H, Abrams KR, Amonkar MM, Casey M. Adjusting for treatment switching in the METRIC study shows further improved overall survival with trametinib compared with chemotherapy. Cancer Med. 2016 May;5(5):806-15. doi: 10.1002/cam4.643. Epub 2016 Jan 27.
- Schadendorf D, Amonkar MM, Milhem M, Grotzinger K, Demidov LV, Rutkowski P, Garbe C, Dummer R, Hassel JC, Wolter P, Mohr P, Trefzer U, Lefeuvre-Plesse C, Rutten A, Steven N, Ullenhag G, Sherman L, Wu FS, Patel K, Casey M, Robert C. Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study. Ann Oncol. 2014 Mar;25(3):700-706. doi: 10.1093/annonc/mdt580. Epub 2014 Feb 6.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 114267
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Melanoma
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H. Lee Moffitt Cancer Center and Research InstituteTurnstone Biologics, Corp.RecruitingMetastatic Melanoma | Conjunctival Melanoma | Ocular Melanoma | Unresectable Melanoma | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Iris Melanoma | Acral Melanoma | Non-Cutaneous MelanomaUnited States
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University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Mucosal Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Ciliary Body and Choroid Melanoma, Small Size | Iris Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage... and other conditionsUnited States
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National Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IA Melanoma | Stage IB Melanoma | Stage IIA MelanomaUnited States
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Rutgers, The State University of New JerseyNational Cancer Institute (NCI); University of VirginiaCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage III Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin Melanoma | Stage 0 Skin Melanoma | Stage I Skin Melanoma | Stage II Skin MelanomaUnited States
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MelanomaPRO, RussiaRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma, Stage II | Melanoma, Uveal | Melanoma in Situ | Melanoma, OcularRussian Federation
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Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IIA MelanomaUnited States
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National Cancer Institute (NCI)CompletedStage IV Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Iris Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIB Melanoma | Stage IIC MelanomaUnited States
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Roswell Park Cancer InstituteNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IV Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIIA Intraocular Melanoma | Stage IIIB Intraocular Melanoma | Stage...United States
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Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
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BiocadRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma Metastatic | Melanoma Unresectable | Melanoma AdvancedIndia, Russian Federation, Belarus
Clinical Trials on GSK1120212
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Novartis PharmaceuticalsTerminatedCancerFrance, United States, Netherlands, Canada, Taiwan, Korea, Republic of
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National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Metastatic Malignant Neoplasm in the Liver | Unresectable Solid NeoplasmUnited States, Canada
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National Cancer Institute (NCI)Children's Oncology GroupActive, not recruitingJuvenile Myelomonocytic Leukemia | Neurofibromatosis Type 1United States
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National Cancer Institute (NCI)CompletedLocally Advanced Epithelioid Hemangioendothelioma | Metastatic Epithelioid Hemangioendothelioma | Unresectable Epithelioid HemangioendotheliomaUnited States
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Jonsson Comprehensive Cancer CenterNovartis; Stand Up To Cancer; Prostate Cancer FoundationActive, not recruitingMetastatic Prostate Carcinoma | Recurrent Prostate Carcinoma | Stage IV Prostate Cancer | Hormone-Resistant Prostate CancerUnited States
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National Cancer Institute (NCI)CompletedRefractory Plasma Cell Myeloma | Recurrent Plasma Cell MyelomaCanada
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National Cancer Institute (NCI)CompletedStage IV Uveal Melanoma AJCC v7 | Recurrent Uveal MelanomaUnited States, France, United Kingdom
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National Cancer Institute (NCI)GlaxoSmithKlineCompletedStage IV Breast Cancer | Recurrent Breast Carcinoma | Invasive Breast Carcinoma | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative Breast CarcinomaUnited States
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National Cancer Institute (NCI)TerminatedRecurrent Adult Acute Myeloid Leukemia | Untreated Adult Acute Myeloid LeukemiaUnited States
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University of California, DavisNational Cancer Institute (NCI); Merck Sharp & Dohme LLC; NovartisActive, not recruitingKRAS Gene Mutation | Stage IV Non-Small Cell Lung Cancer AJCC v7 | Recurrent Non-Squamous Non-Small Cell Lung Carcinoma | Metastatic Non-Squamous Non-Small Cell Lung CarcinomaUnited States