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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK1120212 | Experimental | MEK inhibitor |
|
| Chemotherapy | Active Comparator | Investigator Choice of DTIC or paclitaxel |
|
| Crossover | Experimental | MEK inhibitor after documented progression on Chemotherapy Arm |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1120212 | Drug | MEK inhibitor |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases as Assessed by the Investigator and Independent Review | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival in All Participants | 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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Inclusion Criteria:
Exclusion Criteria:
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:
History of interstitial lung disease or pneumonitis
History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):
Evidence of new optic disc cupping.
Intraocular pressure > 21 mm Hg as measured by tonography
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Tucson | Arizona | 85724-5024 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | 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. | ||
| 22663011 | Result | 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. | |
| 30690294 |
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Participants (par.) were stratified for lactate dehydrogenase and prior CT for advanced or metastatic disease. 1059 par. were screened and 322 were enrolled to receive trametinib (214 par.) or CT (108 par.) until disease progression, death, or withdrawal. Par. randomized to CT were allowed to cross-over to trametinib if disease progressed.
This was a randomized open-label, multi-center Phase III study to evaluate the efficacy and safety of single agent trametinib compared with chemotherapy (CT) (dacarbazine or paclitaxel). Participants (par.) were enrolled by 86 sites in 19 countries from December 2010 to July 2011. Results as of 16 December 2016 data-cut have been presented.
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| ID | Title | Description |
|---|---|---|
| FG000 | Trametinib | Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal. |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Randomization and Crossover Phase |
|
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| Chemotherapy |
| Drug |
Investigator Choice of DTIC or paclitaxel |
|
| Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and Without Prior Chemotherapy as Assessed by the Investigator | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and With Prior Chemotherapy as Assessed by the Investigator | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| Overall Survival in All Participants | Overall survival was defined as the time from the date of randomization to the date of death due to any cause. | Day 1 until death due to any cause (average of 20.3 months) |
| Overall Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases | 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. | Day 1 until death due to any cause (average of 20.3 months) |
| 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 | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| Number of Participants With OR as Assessed by the Investigator and Independent Review | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| Number of BRAF V600E Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| Number of BRAF V600K Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| Number of Participants With OR Following Cross-over to Trametinib | 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. | Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months) |
| 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 | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| 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 | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| DoR for All Confirmed Responders (CR or PR) as Assessed by the Investigator Review | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| DoR for All Confirmed Responders (CR or PR) as Assessed by the Independent Review | 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. | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| DoR for All Responders (CR or PR) Following Cross-over to Trametinib as Assessed by the Investigator | 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. | 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 Following Cross-over to Trametinib as Assessed by the Investigator | 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. | Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months) |
| Fort Myers |
| Florida |
| 33916 |
| United States |
| GSK Investigational Site | Athens | Georgia | 30607 | United States |
| GSK Investigational Site | Marietta | Georgia | 30060 | United States |
| GSK Investigational Site | Iowa City | Iowa | 52242 | United States |
| GSK Investigational Site | Metairie | Louisiana | 70006 | United States |
| GSK Investigational Site | Boston | Massachusetts | 02114 | United States |
| GSK Investigational Site | Morristown | New Jersey | 07962-1956 | United States |
| GSK Investigational Site | Columbus | Ohio | 43210 | United States |
| GSK Investigational Site | Columbia | South Carolina | 29210 | United States |
| GSK Investigational Site | Chattanooga | Tennessee | 37404 | United States |
| GSK Investigational Site | Memphis | Tennessee | 38120 | United States |
| GSK Investigational Site | Nashville | Tennessee | 37203 | United States |
| GSK Investigational Site | Buenos Aires | C1121ABE | Argentina |
| GSK Investigational Site | Garran | Australian Capital Territory | 2606 | Australia |
| GSK Investigational Site | Port Macquarie | New South Wales | 2444 | Australia |
| GSK Investigational Site | Waratah | New South Wales | 2300 | Australia |
| GSK Investigational Site | South Brisbane | Queensland | 4101 | Australia |
| GSK Investigational Site | Townsville | Queensland | 4810 | Australia |
| GSK Investigational Site | Woolloongabba | Queensland | 4102 | Australia |
| GSK Investigational Site | Kurralta Park | South Australia | 5037 | Australia |
| GSK Investigational Site | Woodville | South Australia | 5011 | Australia |
| GSK Investigational Site | Heidelberg | Victoria | 3084 | Australia |
| GSK Investigational Site | Melbourne | Victoria | 3004 | Australia |
| GSK Investigational Site | Graz | 8036 | Austria |
| GSK Investigational Site | Vienna | 1090 | Austria |
| GSK Investigational Site | Brussels | 1200 | Belgium |
| GSK Investigational Site | Charleroi | 6000 | Belgium |
| GSK Investigational Site | Ghent | 9000 | Belgium |
| GSK Investigational Site | Jette | 1090 | Belgium |
| GSK Investigational Site | Kortrijk | 8500 | Belgium |
| GSK Investigational Site | Leuven | 3000 | Belgium |
| GSK Investigational Site | Wilrijk | 2610 | Belgium |
| GSK Investigational Site | Yvoir | 5530 | Belgium |
| GSK Investigational Site | Calgary | Alberta | T2N 4N2 | Canada |
| GSK Investigational Site | Vancouver | British Columbia | V5Z 4E6 | Canada |
| GSK Investigational Site | Halifax | Nova Scotia | B3H 2Y9 | Canada |
| GSK Investigational Site | Hamilton | Ontario | L8V 5C2 | Canada |
| GSK Investigational Site | London | Ontario | N6A 4L6 | Canada |
| GSK Investigational Site | Oshawa | Ontario | L1G 2B9 | Canada |
| GSK Investigational Site | Ottawa | Ontario | K1H 8L6 | Canada |
| GSK Investigational Site | Toronto | Ontario | M5G 2M9 | Canada |
| GSK Investigational Site | Montreal | Quebec | H2L 4M1 | Canada |
| GSK Investigational Site | Montreal | Quebec | H2W 1S6 | Canada |
| GSK Investigational Site | Hradec Králové | 500 05 | Czechia |
| GSK Investigational Site | Ostrava | 708 52 | Czechia |
| GSK Investigational Site | Prague | 128 08 | Czechia |
| GSK Investigational Site | ZlÃn | 76275 | Czechia |
| GSK Investigational Site | Boulogne-Billancourt | 92100 | France |
| GSK Investigational Site | Grenoble | 38043 | France |
| GSK Investigational Site | Montpellier | 34295 | France |
| GSK Investigational Site | Nantes | 44093 | France |
| GSK Investigational Site | Paris | 75475 | France |
| GSK Investigational Site | Pierre-Bénite | 69495 | France |
| GSK Investigational Site | Rennes | 35042 | France |
| GSK Investigational Site | Tours | 37044 | France |
| GSK Investigational Site | Villejuif | 94805 | France |
| GSK Investigational Site | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
| GSK Investigational Site | Mannheim | Baden-Wurttemberg | 68167 | Germany |
| GSK Investigational Site | Tübingen | Baden-Wurttemberg | 72076 | Germany |
| GSK Investigational Site | Munich | Bavaria | 80804 | Germany |
| GSK Investigational Site | Würzburg | Bavaria | 97080 | Germany |
| GSK Investigational Site | Buxtehude | Lower Saxony | 21614 | Germany |
| GSK Investigational Site | Essen | North Rhine-Westphalia | 45122 | Germany |
| GSK Investigational Site | Dresden | Saxony | 01307 | Germany |
| GSK Investigational Site | Lübeck | Schleswig-Holstein | 23538 | Germany |
| GSK Investigational Site | Berlin | 10117 | Germany |
| GSK Investigational Site | Athens | 11527 | Greece |
| GSK Investigational Site | Athens | 185 47 | Greece |
| GSK Investigational Site | Thessaloniki | 564 29 | Greece |
| GSK Investigational Site | Milan | Lombardy | 20132 | Italy |
| GSK Investigational Site | Milan | Lombardy | 20133 | Italy |
| GSK Investigational Site | Milan | Lombardy | 20141 | Italy |
| GSK Investigational Site | Pisa | Tuscany | 56126 | Italy |
| GSK Investigational Site | Christchurch | 8011 | New Zealand |
| GSK Investigational Site | Dunedin | 9016 | New Zealand |
| GSK Investigational Site | Newtown, Wellington | 6002 | New Zealand |
| GSK Investigational Site | Oslo | 0310 | Norway |
| GSK Investigational Site | Poznan | 61-866 | Poland |
| GSK Investigational Site | Warsaw | 02-781 | Poland |
| GSK Investigational Site | Warsaw | 04-125 | Poland |
| GSK Investigational Site | Chelyabinsk | 454087 | Russia |
| GSK Investigational Site | Magnitogorsk | 455001 | Russia |
| GSK Investigational Site | Moscow | 115478 | Russia |
| GSK Investigational Site | Saint Petersburg | 197758 | Russia |
| GSK Investigational Site | Gothenburg | SE-413 45 | Sweden |
| GSK Investigational Site | Linköping | SE-581 85 | Sweden |
| GSK Investigational Site | Lund | SE-221 85 | Sweden |
| GSK Investigational Site | Stockholm | SE-171 76 | Sweden |
| GSK Investigational Site | Uppsala | SE-751 85 | Sweden |
| GSK Investigational Site | Zurich | 8091 | Switzerland |
| GSK Investigational Site | Dnipro | 49102 | Ukraine |
| GSK Investigational Site | Kharkiv | 61070 | Ukraine |
| GSK Investigational Site | Kyiv | 03022 | Ukraine |
| GSK Investigational Site | Kyiv | 03115 | Ukraine |
| GSK Investigational Site | Lviv | 79031 | Ukraine |
| GSK Investigational Site | Sumy | 40005 | Ukraine |
| GSK Investigational Site | Sympheropol | 95023 | Ukraine |
| GSK Investigational Site | Ternopil | 46023 | Ukraine |
| GSK Investigational Site | Uzhhorod | 88017 | Ukraine |
| GSK Investigational Site | Cambridge | Cambridgeshire | CB2 2QQ | United Kingdom |
| GSK Investigational Site | Northwood | Middlesex | HA6 2RN | United Kingdom |
| GSK Investigational Site | Sutton | Surrey | SM2 5PT | United Kingdom |
| GSK Investigational Site | Aberdeen | AB25 2ZN | United Kingdom |
| GSK Investigational Site | Birmingham | B15 2TH | United Kingdom |
| GSK Investigational Site | Chelmsford | CM1 7ET | United Kingdom |
| GSK Investigational Site | Leeds | LS9 7TF | United Kingdom |
| GSK Investigational Site | London | SW3 6JJ | United Kingdom |
| GSK Investigational Site | London | W1G 6AD | United Kingdom |
| GSK Investigational Site | Manchester | M20 4BX | United Kingdom |
| GSK Investigational Site | Oxford | OX3 7LJ | United Kingdom |
| GSK Investigational Site | Southampton | SO16 6YD | United Kingdom |
| Derived |
| 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. |
| 27172483 | Derived | 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. |
| 26446943 | Derived | 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. |
| 24504441 | Derived | 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. |
| FG001 | Chemotherapy | Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. |
| FG002 | Cross-over From Chemotherapy to Trametinib | Participants randomized to chemotherapy and who did not receive subsequent anti-cancer therapy after discontinuing chemotherapy were allowed to cross-over to Trametinib and received 2 mg tablet once daily until disease progression, death or withdrawal. |
|
| COMPLETED | Par. completed the study as they died during the conduct of the study. |
|
| NOT COMPLETED |
|
|
| Cross-over Phase |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Trametinib | Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal. |
| BG001 | Chemotherapy | Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Progression-free Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases as Assessed by the Investigator and Independent Review | 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. | Primary Efficacy Population | Posted | Median | 95% Confidence Interval | Months | 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 | Progression-free Survival in All Participants | 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. | ITT Population | Posted | Median | 95% Confidence Interval | Months | 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 | PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and Without Prior Chemotherapy as Assessed by the Investigator | 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. | Primary Efficacy Population | Posted | Median | 95% Confidence Interval | Months | 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 | PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and With Prior Chemotherapy as Assessed by the Investigator | 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. | Primary Efficacy Population | Posted | Median | 95% Confidence Interval | Months | 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 | Overall Survival in All Participants | Overall survival was defined as the time from the date of randomization to the date of death due to any cause. | ITT Population | Posted | Median | 95% Confidence Interval | Months | Day 1 until death due to any cause (average of 20.3 months) |
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| Secondary | Overall Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases | 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. | Primary Efficacy Population | Posted | Median | 95% Confidence Interval | Months | Day 1 until death due to any cause (average of 20.3 months) |
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| Secondary | 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 | 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. | Primary Efficacy Population | Posted | Number | Participants | 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 | Number of Participants With OR as Assessed by the Investigator and Independent Review | 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. | ITT Population | Posted | Number | Participants | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of BRAF V600E Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator | 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. | ITT Population | Posted | Number | Participants | 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 | Number of BRAF V600K Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator | 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. | ITT Population | Posted | Number | Participants | 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 | Number of Participants With OR Following Cross-over to Trametinib | 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. | Cross-over Population | Posted | Number | Participants | 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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| Secondary | 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 | 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. | Primary Efficacy Population | Posted | Median | 95% Confidence Interval | Months | 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 | 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 | 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. | Primary Efficacy Population | Posted | Median | 95% Confidence Interval | Months | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | DoR for All Confirmed Responders (CR or PR) as Assessed by the Investigator Review | 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. | ITT Population | Posted | Median | 95% Confidence Interval | Months | Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | DoR for All Confirmed Responders (CR or PR) as Assessed by the Independent Review | 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. | ITT Population | Posted | Median | 95% Confidence Interval | Months | 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 | DoR for All Responders (CR or PR) Following Cross-over to Trametinib as Assessed by the Investigator | 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. | Cross-over Population | Posted | Median | 95% Confidence Interval | Months | 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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| Secondary | PFS Following Cross-over to Trametinib as Assessed by the Investigator | 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. | Cross-over Population | Posted | Median | 95% Confidence Interval | Months | Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months) |
|
|
Participants were analyzed from the first dose of study medication to 28 days after discontinuation of study medication (average of 20.3 months in the Randomization Phase and 18.3 months in the Cross-over Phase).
Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all randomized participants included in the study who received at least one dose of study medication.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Trametinib | Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal. | 172 | 211 | 52 | 211 | 207 | 211 |
| EG001 | Chemotherapy | Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. | 22 | 99 | 19 | 99 | 88 | 99 |
| EG002 | Cross-over From Chemotherapy to Trametinib | Participants randomized to chemotherapy and who did not receive subsequent anti-cancer therapy after discontinuing chemotherapy were allowed to cross-over to Trametinib and received 2 mg tablet once daily until disease progression, death or withdrawal. | 53 | 70 | 18 | 70 | 66 | 70 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Eye infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Klebsiella infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Localized infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Lymphangitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Axillary pain | General disorders | MedDRA | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA | Systematic Assessment |
| |
| Edema | General disorders | MedDRA | Systematic Assessment |
| |
| Pain | General disorders | MedDRA | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA | Systematic Assessment |
| |
| Hemoglobin decreased | Investigations | MedDRA | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastric hemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Conduction disorder | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Gallbladder obstruction | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA | Systematic Assessment |
| |
| Corneal graft rejection | Immune system disorders | MedDRA | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Ischemic stroke | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Testicular pain | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
| |
| Pericarditis | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Eyelid ptosis | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Retinal vein occlusion | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Gastritis erosive | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Clostridial infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Wound infection staphylococcal | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
| |
| Rectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
| |
| Carotid artery dissection | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Ureterolithiasis | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Large intestinal ulcer | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Infected seroma | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Infected skin ulcer | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Streptococcal sepsis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Lymphedema | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Inflammation | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Nail infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C560077 | trametinib |
| D004358 | Drug Therapy |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
Not provided
Not provided
| Withdrew Consent |
|
| Study closed/ terminated |
|
| Male |
|
| White - White/Caucasian/European Heritage |
|
| White - Mixed Race |
|
| Log Rank | <0.0001 | P-value from a stratified log-rank test was adjusted for prior chemotherapy for advanced or metastatic disease and Baseline lactate dehydrogenase. | Hazard Ratio (HR) | 0.41 | 2-Sided | 95 | 0.29 | 0.60 | Independent Review PFS. HR <1 indicates a lower risk with Trametinib compared with CT. HR from a stratified log-rank test was adjusted for prior chemotherapy for advanced or metastatic disease and Baseline lactate dehydrogenase. | Superiority |
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| Units | Counts |
|---|---|
| Participants |
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| OG001 | Chemotherapy | Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. |
|
|
| OG001 | Chemotherapy | Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. |
|
|
| OG001 |
| Chemotherapy |
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. |
|
|
| OG001 |
| Chemotherapy |
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. |
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