GSK1120212 vs Chemotherapy in Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma

• ClinicalTrials.gov Identifier: NCT01245062
• Recruitment Status: Completed
• First Posted: November 22, 2010
• Results First Posted: March 15, 2013
• Last Update Posted: April 5, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

This is a two-arm, open-label, randomized Phase III study comparing single agent GSK1120212 to chemotherapy (either dacarbazine or paclitaxel) in subjects with Stage IIIc or Stage IV malignant cutaneous melanoma. All subjects must have a BRAF mutation-positive tumour sample. Subjects who have received up to one prior regimen of chemotherapy in the advanced or metastatic melanoma setting will be enrolled into the study. Subjects with any prior BRAF or MEK inhibitor use will be excluded. Approximately 297 subjects will be enrolled with 2:1 randomization (198 subjects into the GSK1120212 arm and 99 subjects into the chemotherapy arm). The primary endpoint for the statistical analysis will be a comparison of progression free survival for subjects receiving GSK1120212 compared to chemotherapy. Subjects who have progression on chemotherapy will be offered the option to receive GSK1120212.

Condition or disease	Intervention/treatment	Phase
Melanoma	Drug: GSK1120212; Drug: Chemotherapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 322 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Randomized, Open-label Study Comparing GSK1120212 to Chemotherapy in Subjects With Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma
• Actual Study Start Date: November 22, 2010
• Actual Primary Completion Date: October 26, 2011
• Actual Study Completion Date: December 16, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: GSK1120212; MEK inhibitor	Drug: GSK1120212; MEK inhibitor
Active Comparator: Chemotherapy; Investigator Choice of DTIC or paclitaxel	Drug: Chemotherapy; Investigator Choice of DTIC or paclitaxel
Experimental: Crossover; MEK inhibitor after documented progression on Chemotherapy Arm	Drug: GSK1120212; MEK inhibitor

Outcome Measures

Primary Outcome Measures :

1. 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) ]
   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.

Secondary Outcome Measures :

1. 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) ]
   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.
2. 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) ]
   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.
3. 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) ]
   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.
4. Overall Survival in All Participants [ Time Frame: Day 1 until death due to any cause (average of 20.3 months) ]
   Overall survival was defined as the time from the date of randomization to the date of death due to any cause.
5. 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) ]
   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.
6. 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) ]
   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.
7. 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) ]
   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.
8. 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) ]
   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.
9. 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) ]
   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.
10. 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) ]
    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.
11. 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) ]
    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.
12. 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) ]
    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.
13. 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) ]
    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.
14. 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) ]
    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.
15. 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) ]
    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.
16. 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) ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Arizona

GSK Investigational Site

Tucson, Arizona, United States, 85724-5024

United States, Florida

GSK Investigational Site

Fort Myers, Florida, United States, 33916

United States, Georgia

GSK Investigational Site

Athens, Georgia, United States, 30607

GSK Investigational Site

Marietta, Georgia, United States, 30060

United States, Iowa

GSK Investigational Site

Iowa City, Iowa, United States, 52242

United States, Louisiana

GSK Investigational Site

Metairie, Louisiana, United States, 70006

United States, Massachusetts

GSK Investigational Site

Boston, Massachusetts, United States, 02114

United States, New Jersey

GSK Investigational Site

Morristown, New Jersey, United States, 07962-1956

United States, Ohio

GSK Investigational Site

Columbus, Ohio, United States, 43210

United States, South Carolina

GSK Investigational Site

Columbia, South Carolina, United States, 29210

United States, Tennessee

GSK Investigational Site

Chattanooga, Tennessee, United States, 37404

GSK Investigational Site

Memphis, Tennessee, United States, 38120

GSK Investigational Site

Nashville, Tennessee, United States, 37203

Argentina

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Argentina, C1121ABE

Australia, Australian Capital Territory

GSK Investigational Site

Garran, Australian Capital Territory, Australia, 2606

Australia, New South Wales

GSK Investigational Site

Port Macquarie, New South Wales, Australia, 2444

GSK Investigational Site

Waratah, New South Wales, Australia, 2300

Australia, Queensland

GSK Investigational Site

South Brisbane, Queensland, Australia, 4101

GSK Investigational Site

Townsville, Queensland, Australia, 4810

GSK Investigational Site

Woolloongabba, Queensland, Australia, 4102

Australia, South Australia

GSK Investigational Site

Kurralta Park, South Australia, Australia, 5037

GSK Investigational Site

Woodville, South Australia, Australia, 5011

Australia, Victoria

GSK Investigational Site

Heidelberg, Victoria, Australia, 3084

GSK Investigational Site

Melbourne, Victoria, Australia, 3004

Austria

GSK Investigational Site

Graz, Austria, 8036

GSK Investigational Site

Wien, Austria, 1090

Belgium

GSK Investigational Site

Brussels, Belgium, 1200

GSK Investigational Site

Charleroi, Belgium, 6000

GSK Investigational Site

Gent, Belgium, 9000

GSK Investigational Site

Jette, Belgium, 1090

GSK Investigational Site

Kortrijk, Belgium, 8500

GSK Investigational Site

Leuven, Belgium, 3000

GSK Investigational Site

Wilrijk, Belgium, 2610

GSK Investigational Site

Yvoir, Belgium, 5530

Canada, Alberta

GSK Investigational Site

Calgary, Alberta, Canada, T2N 4N2

Canada, British Columbia

GSK Investigational Site

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Nova Scotia

GSK Investigational Site

Halifax, Nova Scotia, Canada, B3H 2Y9

Canada, Ontario

GSK Investigational Site

Hamilton, Ontario, Canada, L8V 5C2

GSK Investigational Site

London, Ontario, Canada, N6A 4L6

GSK Investigational Site

Oshawa, Ontario, Canada, L1G 2B9

GSK Investigational Site

Ottawa, Ontario, Canada, K1H 8L6

GSK Investigational Site

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

GSK Investigational Site

Montreal, Quebec, Canada, H2L 4M1

GSK Investigational Site

Montreal, Quebec, Canada, H2W 1S6

Czechia

GSK Investigational Site

Hradec Kralove, Czechia, 500 05

GSK Investigational Site

Ostrava, Czechia, 708 52

GSK Investigational Site

Praha 2, Czechia, 128 08

GSK Investigational Site

Zlin, Czechia, 76275

France

GSK Investigational Site

Boulogne-Billancourt, France, 92100

GSK Investigational Site

Grenoble, France, 38043

GSK Investigational Site

Montpellier, France, 34295

GSK Investigational Site

Nantes, France, 44093

GSK Investigational Site

Paris Cedex 10, France, 75475

GSK Investigational Site

Pierre-Benite cedex, France, 69495

GSK Investigational Site

Rennes, France, 35042

GSK Investigational Site

Tours, France, 37044

GSK Investigational Site

Villejuif, France, 94805

Germany

GSK Investigational Site

Heidelberg, Baden-Wuerttemberg, Germany, 69120

GSK Investigational Site

Mannheim, Baden-Wuerttemberg, Germany, 68167

GSK Investigational Site

Tuebingen, Baden-Wuerttemberg, Germany, 72076

GSK Investigational Site

Muenchen, Bayern, Germany, 80804

GSK Investigational Site

Wuerzburg, Bayern, Germany, 97080

GSK Investigational Site

Buxtehude, Niedersachsen, Germany, 21614

GSK Investigational Site

Essen, Nordrhein-Westfalen, Germany, 45122

GSK Investigational Site

Dresden, Sachsen, Germany, 01307

GSK Investigational Site

Luebeck, Schleswig-Holstein, Germany, 23538

GSK Investigational Site

Berlin, Germany, 10117

Greece

GSK Investigational Site

Athens, Greece, 11527

GSK Investigational Site

Athens, Greece, 185 47

GSK Investigational Site

Thessaloniki, Greece, 564 29

Italy

GSK Investigational Site

Milano, Lombardia, Italy, 20132

GSK Investigational Site

Milano, Lombardia, Italy, 20133

GSK Investigational Site

Milano, Lombardia, Italy, 20141

GSK Investigational Site

Pisa, Toscana, Italy, 56126

New Zealand

GSK Investigational Site

Christchurch, New Zealand, 8011

GSK Investigational Site

Dunedin, New Zealand, 9016

GSK Investigational Site

Newtown, Wellington, New Zealand, 6002

Norway

GSK Investigational Site

Oslo, Norway, 0310

Poland

GSK Investigational Site

Poznan, Poland, 61-866

GSK Investigational Site

Warszawa, Poland, 02-781

GSK Investigational Site

Warszawa, Poland, 04-125

Russian Federation

GSK Investigational Site

Chelyabinsk, Russian Federation, 454087

GSK Investigational Site

Magnitogorsk, Russian Federation, 455001

GSK Investigational Site

Moscow, Russian Federation, 115478

GSK Investigational Site

St. Petersburg, Russian Federation, 197758

Sweden

GSK Investigational Site

Goteborg, Sweden, SE-413 45

GSK Investigational Site

Linkoping, Sweden, SE-581 85

GSK Investigational Site

Lund, Sweden, SE-221 85

GSK Investigational Site

Stockholm, Sweden, SE-171 76

GSK Investigational Site

Uppsala, Sweden, SE-751 85

Switzerland

GSK Investigational Site

Zurich, Switzerland, 8091

Ukraine

GSK Investigational Site

Dnepropetrovsk, Ukraine, 49102

GSK Investigational Site

Kharkiv, Ukraine, 61070

GSK Investigational Site

Kyiv, Ukraine, 03022

GSK Investigational Site

Kyiv, Ukraine, 03115

GSK Investigational Site

Lviv, Ukraine, 79031

GSK Investigational Site

Sumy, Ukraine, 40005

GSK Investigational Site

Sympheropol, Ukraine, 95023

GSK Investigational Site

Ternopil, Ukraine, 46023

GSK Investigational Site

Uzhgorod, Ukraine, 88017

United Kingdom

GSK Investigational Site

Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ

GSK Investigational Site

Northwood, Middlesex, United Kingdom, HA6 2RN

GSK Investigational Site

Sutton, Surrey, United Kingdom, SM2 5PT

GSK Investigational Site

Aberdeen, United Kingdom, AB25 2ZN

GSK Investigational Site

Birmingham, United Kingdom, B15 2TH

GSK Investigational Site

Chelmsford, United Kingdom, CM1 7ET

GSK Investigational Site

Leeds, United Kingdom, LS9 7TF

GSK Investigational Site

London, United Kingdom, SW3 6JJ

GSK Investigational Site

London, United Kingdom, W1G 6AD

GSK Investigational Site

Manchester, United Kingdom, M20 4BX

GSK Investigational Site

Oxford, United Kingdom, OX3 7LJ

GSK Investigational Site

Southampton, United Kingdom, SO16 6YD

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Publications of Results:

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.

Other Publications:

KT Flaherty, C Robert, P Hersey, P Nathan, C Garbe, M Milhem, L Demidov, J Hassel, P Rutkowski, P Mohr, R Dummer, U Trefzer, JMG Larkin, J Utikal, B Dreno, M Nyakas, MR Middleton, JC Becker, M Casey, LJ Sherman, FS Wu, D Ouellet, AM Martin, K Patel, & D S. MEK inhibition improves survival in Melanoma with activating BRAF Mutations. [N Engl J Med]. 2012;367:107-14.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01245062
• Other Study ID Numbers: 114267
• First Posted: November 22, 2010
• Results First Posted: March 15, 2013
• Last Update Posted: April 5, 2018
• Last Verified: January 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

MEK inhibitor; Cancer; Metastatic Melanoma; BRAF mutant metastatic melanoma; GSK1120212

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Trametinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action