Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma

The NEMO Trial (NRAS Melanoma and MEK Inhibitor):A Randomized Phase III, Open Label, Multicenter, Two-arm Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Patients With Advanced Unresectable or Metastatic NRAS Mutation-positive Melanoma

Two-arm, randomized, prospective, open-label, multi-center, phase III study to compare the efficacy and safety of MEK162 (45 mg BID) versus dacarbazine (1000 mg/m2 IV every 3 weeks) in patients with advanced (Stage IIIC) unresectable or metastatic (Stage IV) NRAS Q61 mutation-positive cutaneous or unknown primary melanoma. The mutation analysis will be performed at a central laboratory. Only those patients with Q61 mutation per central laboratory and meet all eligibility criteria will be randomized. A total of 393 patients will be randomized 2:1 to receive either MEK162 or dacarbazine. Patients will be stratified according to AJCC stage (IIIC, IVM1a, and IVM1b versus IVM1c), ECOG Performance status (0 versus 1) and any prior number of lines of immunotherapy (immunotherapies versus none). This study will use an Interactive Response Technology (IRT). The primary end point of the study is progression-free survival. Key secondary end point is overall survival

Study Overview

• Status: Completed
• Conditions: Metastatic or Unresectable Cutaneous Melanoma
• Intervention / Treatment: Drug: MEK162; Drug: Dacarbazine

• Study Type: Interventional
• Enrollment (Actual): 402
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABE
    • Fundacion Cidea
  • Ciudad Autónoma DE Buenosaires
    • Buenos Aires, Ciudad Autónoma DE Buenosaires, Argentina, C1050AAK
      • Sanatorio de La Providencia
  • RÍO Negro
    • Viedma, RÍO Negro, Argentina, 08500
      • Centro de Investigación Clínica ? Clínica Viedma
  • Santa FE
    • Rosario, Santa FE, Argentina, S2000KZE
      • Centro Oncologico de Rosario
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse Hospital
    • Gateshead, New South Wales, Australia, 02290
      • Lake Macquarie Private Hospital
    • North Sydney, New South Wales, Australia, 2060
      • Melanoma Institute Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 05000
      • Royal Adelaide Hospital
• Austria
  • Salzburg, Austria, 05020
    • Salzburger Landeskliniken
  • Vienna, Austria, 01090
    • Allgemeines Krankenhaus der Stadt Wien
  • Steiermark
    • Graz, Steiermark, Austria, 08036
      • LKH-Universitätsklinikum Klinikum Graz
  • Tirol
    • Innsbruck, Tirol, Austria, 06020
      • Universitätsklinikum Innsbruck
• Belgium
  • Leuven, Belgium, 03000
    • Uz Gasthuisberg
  • Liege, Belgium, 04000
    • CHU Sart Tilman
  • Antwerpen
    • Wilrijk, Antwerpen, Belgium, 2610
      • Sint-Augustinuskliniek
• Brazil
  • Rio de Janeiro, Brazil, 20220410
    • INCA Instituto Nacional de Cancer
  • Sao Paulo, Brazil, 01321-001
    • Hospital Sao Jose
  • RIO Grande DO SUL
    • Passo Fundo, RIO Grande DO SUL, Brazil, 99010-260
      • Hospital de Clínicas de Passo Fundo
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90035-903
      • Hospital Moinhos de Vento
    • Porto Alegre, RIO Grande DO SUL, Brazil, 90560-030
      • Hospital Moinhos de Vento
• Canada
  • Quebec, Canada, G1R 2J6
    • CHU de Quebec - L'Hotel-Dieu de Quebec
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Alberta Health Services - Cross Cancer Institute
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Center / Royal Victoria Hospital
• Czechia
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha 2, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
  • Jihomoravský KRAJ
    • Brno, Jihomoravský KRAJ, Czechia, 656 53
      • Mou/Mmci - Ppds
• France
  • Bordeaux, France, 33000
    • Hôpital Saint-André
  • Boulogne Billancourt, France, 92100
    • Centre Hospitalier Universitaire Ambroise Pare
  • Le Mans, France, 72037
    • Centre Hospitalier Le Mans
  • Marseille, France, 13385
    • Hopitaux de La Timone
  • Nice, France, 06202
    • Groupe Hospitalier Archet I Et II
  • Paris, France, 75010
    • Hopital Saint Louis
  • Pierre Benite, France, 69495
    • Service de PneumologieCHU Lyon Sud
  • Reims, France, 51092
    • Hôpital Robert Debré
  • Rouen, France, 76031
    • Centre Hospitalier Universitaire Hôpitaux de Rouen
  • Maine-et-loire
    • Angers, Maine-et-loire, France, 49033
      • CHU Angers
  • Nord
    • Lille, Nord, France, 59037
      • CHRU de Lille - Hôpital Huriet
  • Rhône
    • Lyon, Rhône, France, 69373
      • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus an der TU Dresden
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Gera, Germany, 07548
    • Srh Wald-Klinikum Gera Gmbh
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover (Hannover Medical School)
  • Heidelberg, Germany, 69120
    • University Clinic Heidelberg - PPDS
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein
  • Koeln, Germany, 50937
    • Uniklinik Köln
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein
  • Münster, Germany, 48157
    • Fachklinik Hornheide
  • Nürnberg, Germany, 90419
    • Klinikum Nuernberg Nord
  • Tübingen, Germany, 72076
    • Universitatsklinikum Tubingen
  • Ulm, Germany, 89081
    • Universit*ätsklinikum Ulm
  • Baden-württemberg
    • Freiburg im Breisgau, Baden-württemberg, Germany, 79104
      • Universitaetsklinikum Freiburg
    • Mannheim, Baden-württemberg, Germany, 68135
      • Klinikum Mannheim Universitätsklinikum gGmbH
  • Bayern
    • München, Bayern, Germany, 80337
      • LMU Klinikum der Universität München
    • Regensburg, Bayern, Germany, 93053
      • University Clinic Regensburg - PPDS
    • Würzburg, Bayern, Germany, 97080
      • Universitatsklinikum Wurzburg
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Universitatsklinikum Frankfurt
    • Frankfurt, Hessen, Germany, 60590
      • Institut für Diagnostische und Interventionelle Radiologie Frankfurt
  • Niedersachsen
    • Buxtehude, Niedersachsen, Germany, 21614
      • Elben Klinken Stade Buxtehude
  • Nordrhein-westfalen
    • Minden, Nordrhein-westfalen, Germany, 32429
      • Johannes Wesling Klinikum Minden
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig
  • Sachsen-anhalt
    • Quedlinburg, Sachsen-anhalt, Germany, 06484
      • Klinikum Dorothea Christiane Erxleben Quedlinburg GmbH
  • Schleswig-holstein
    • Berlin, Schleswig-holstein, Germany, 10117
      • Charité Campus Mitte
  • Thüringen
    • Erfurt, Thüringen, Germany, 99089
      • Helios Klinikum Erfurt
• Greece
  • Athens, Greece, 115 27
    • Laiko General Hospital of Athens
• Hungary
  • Budapest, Hungary, H-1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 01062
    • Magyar Honvedseg Egeszsegugyi Kozpont
  • Kaposvár, Hungary, 07400
    • Somogy Megyei Kaposi Mor Oktato Korhaz
  • Szolnok, Hungary, 05004
    • Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelointézet
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center - PPDS
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center - PPDS
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center - PPDS
• Italy
  • Bari, Italy, 70126
    • IRCCS Giovanni Paolo II Istituto Oncologico
  • Bergamo, Italy, 24129
    • ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII
  • Genova, Italy, 16132
    • IRCCS Az. Osp. Universitaria San Martino- IST
  • Milano, Italy, 20132
    • Ospedale San Raffaele S.r.l. - PPDS
  • Milano, Italy, 20133
    • Fondazione IRCCS 'Istituto Nazionale dei Tumori' di Milano
  • Roma, Italy, 00144
    • Istituto Nazionale Tumori Regina Elena
  • Siena, Italy, 53100
    • Azienza Ospedaliera Universitaria Senese
  • Torino, Italy, 10126
    • A.O.U. Città della Salute e della Scienza di Torino - Presidio S. Lazzaro
  • Campania
    • Napoli, Campania, Italy, 80138
      • AOU dell'Università degli Studi della Campania Luigi Vanvitelli
  • Lazio
    • Roma, Lazio, Italy, 00167
      • Istituto Dermopatico Dell'Immacolata Irccs
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
  • Naples
    • Napoli, Naples, Italy, 80131
      • Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Istituto Oncologico Veneto - I.R.C.C.S.
• Japan
  • Chuo-ku, Japan, 1040045
    • National Cancer Center Hospital
  • Hirakata-city, Japan, 573-1191
    • Kansai Medical University Hospital
  • Nagano
    • Matsumoto, Nagano, Japan, 390-8621
      • Shinshu University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - PPDS
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center - PPDS
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital Yonsei University Health System - PPDS
• Netherlands
  • Zwolle, Netherlands, 8025 AB
    • Isala Klinieken
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud University Nijmegen Medical Centre
  • Noord-holland
    • Amsterdam, Noord-holland, Netherlands, 1066 CX
      • Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
  • Zuid-holland
    • Leiden, Zuid-holland, Netherlands, 2333ZA
      • Leids Universitair Medisch Centrum
• Poland
  • Warszawa, Poland, 02-676
    • Lux Med
  • Warszawa, Poland, 02-781
    • Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-673
      • Centrum Medyczne MAVIT Sp. z o.o.
• Portugal
  • Almada, Portugal, 2801-951
    • Hospital Garcia de Orta*E.P.E.
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria
  • Porto, Portugal, 4200-072
    • Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
  • Lisboa
    • Lisbon, Lisboa, Portugal, 1099-023
      • Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Russian Oncology Research Center n a N N Blokhin
  • Ryazan, Russian Federation, 390011
    • Ryazan Regional Clinical Oncology Dispensary
  • St. Petersburg, Russian Federation, 197758
    • Scientific Research Institute of Oncology n.a. N.N. Petrov
• Slovakia
  • Bratislava, Slovakia, 833 01
    • Narodny onkologicky ustav
• South Africa
  • FREE State
    • Bloemfontein, FREE State, South Africa, 09301
      • University of The Free State
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 02196
      • Sandton Oncology Medical Group
    • Johannesburg, Gauteng, South Africa, 02199
      • Sandton Oncology Medical Research
    • Pretoria, Gauteng, South Africa, 00002
      • Steve Biko Academic Hospital
    • Pretoria, Gauteng, South Africa, 00027
      • Mary Potter Oncology Centre
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Barcelona, Spain, 08907
    • Ico L'Hospitalet - Hospital Duran I Reynals
  • Gran Canaria, Spain, 35001
    • Complejo Hospitalario Universitario Insular - Materno Infantil
  • La Coruna, Spain, 15006
    • Hospital Universitario A Coruña
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro - CIOCC
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Toledo, Spain, 45004
    • Hospital Virgen De La Salud
  • Valencia, Spain, 46009
    • Fundacion Instituto Valenciano de Oncologia
  • Valencia, Spain, 46014
    • Consorcio Hospital General Universitario de Valencia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Ico L'Hospitalet - Hospital Duran I Reynals
  • Málaga
    • Malaga, Málaga, Spain, 29010
      • Hospital Regional Universitario de Malaga Hospital General
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad Navarra
• Sweden
  • Lund, Sweden, 221 85
    • Skånes universitetssjukhus Lund
  • Skane LAN
    • Lund, Skane LAN, Sweden
      • Skånes universitetssjukhus Lund
• Switzerland
  • Genève, Switzerland, 01211
    • Hopitaux Universitaires de Geneve
  • Lausanne, Switzerland, 01011
    • Centre Hospitalier Universitaire Vaudois
  • Zürich (DE)
    • Zurich, Zürich (DE), Switzerland, 08091
      • Universitätsspital Zürich
• Turkey
  • Adana, Turkey, 01230
    • Adana Ba?kent Hastanesi K??la Yerle?kesi
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty
  • Ankara, Turkey, 06490
    • Baskent University Medical Faculty Ankara Hospital
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa Medical Faculty Hospital
  • Izmir
    • Bornova, Izmir, Turkey, 35100
      • Ege University Medical Faculty
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St James s Institute of Clinical Oncology
  • Wirral, United Kingdom, CH63 4JY
    • Clatterbridge Hospital
  • Bristol, CITY OF
    • Bristol, Bristol, CITY OF, United Kingdom, BS2 8ED
      • Bristol Haematology and Oncology Centre
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital
  • EAST Sussex
    • Brighton, EAST Sussex, United Kingdom, BN2 5BE
      • The Royal Sussex County Hospital
  • Essex
    • Chelmsford, Essex, United Kingdom, CM1 7ET
      • Broomfield Hospital
  • Glamorgan
    • Swansea, Glamorgan, United Kingdom, SA2 8QA
      • Singleton Hospital - PPDS
  • Lancashire
    • Preston, Lancashire, United Kingdom, PR2 9HT
      • Royal Preston Hospital
  • London, CITY OF
    • London, London, CITY OF, United Kingdom, SW3 6JJ
      • Royal Marsden Hospital - Surrey
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Florida Cancer Specialists
    • Bonita Springs, Florida, United States, 34135
      • Florida Cancer Specialists
    • Bradenton, Florida, United States, 34209
      • Florida Cancer Specialists
    • Brandon, Florida, United States, 33511
      • Florida Cancer Specialists
    • Cape Coral, Florida, United States, 33914
      • Florida Cancer Specialists
    • Clearwater, Florida, United States, 33761
      • Florida Cancer Specialists
    • Clearwater, Florida, United States, 33756
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33905
      • Florida Cancer Specialists
    • Fort Myers, Florida, United States, 33908
      • Florida Cancer Specialists
    • Gainesville, Florida, United States, 32605
      • Florida Cancer Specialists
    • Hudson, Florida, United States, 34667
      • Florida Cancer Specialists
    • Inverness, Florida, United States, 34453
      • Florida Cancer Specialists
    • Largo, Florida, United States, 33770
      • Florida Cancer Specialists
    • Largo, Florida, United States, 33777
      • Florida Cancer Specialists
    • Naples, Florida, United States, 34102
      • Florida Cancer Specialists
    • Naples, Florida, United States, 34119
      • Florida Cancer Specialists
    • New Port Richey, Florida, United States, 34655
      • Florida Cancer Specialists
    • Orange City, Florida, United States, 32763
      • Florida Cancer Specialists
    • Orlando, Florida, United States, 32806
      • Florida Cancer Specialists
    • Port Charlotte, Florida, United States, 33980
      • Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33707
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
    • Sarasota, Florida, United States, 34236
      • Florida Cancer Specialists
    • Spring Hill, Florida, United States, 34608
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33607
      • Florida Cancer Specialists
    • Tampa, Florida, United States, 33613
      • Florida Cancer Specialists
    • Tavares, Florida, United States, 32778
      • Florida Cancer Specialists
    • Venice, Florida, United States, 34285
      • Florida Cancer Specialists
    • Venice, Florida, United States, 34292
      • Florida Cancer Specialists
  • Illinois
    • Niles, Illinois, United States, 60714
      • Oncology Specialists, SC
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, SC
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Goshen Center for Cancer Care
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Harry and Jeannette Weinberg Cancer Institute @Franklin Square
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Kresge Eye Institute
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201
      • Kresge Eye Institute
    • Farmington Hills, Michigan, United States, 48334
      • Karmanos Cancer Institute of Farmington Hills
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
    • Voorhees, New Jersey, United States, 08043
      • Cooper University Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University James Cancer Hospital
    • Columbus, Ohio, United States, 43221
      • The Ohio State University Martha Morehouse Medical Plaza
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97201
      • OHSU Knight Cancer Institute
    • Portland, Oregon, United States, 97239
      • OHSU Center for Health and Healing
    • Portland, Oregon, United States, 97239
      • OHSU
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest Region Oncology/Hematology
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Cancer Center Associates - Medical Oncology
    • Allentown, Pennsylvania, United States, 18104
      • St. Luke's Cancer Center - Allentown Campus
    • Allentown, Pennsylvania, United States, 18104
      • St. Luke's Hospital - Allentown Campus
    • Bethlehem, Pennsylvania, United States, 18015
      • Cancer Center Associates - Medical Oncology
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Hospital - Bethlehem Campus
    • Easton, Pennsylvania, United States, 18045
      • St. Luke's Cancer Center - Anderson Campus
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Medical Oncology
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania, Perelman Center for Advanced Medicine
    • Quakertown, Pennsylvania, United States, 18951
      • St. Luke's Hospital - Quakertown Campus
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology-Austin Central
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center at Dallas
    • Dallas, Texas, United States, 75230
      • Elliot J. Ginchansky, MD, PA
    • Dallas, Texas, United States, 75231
      • Dennis B. Kay
    • Dallas, Texas, United States, 75235
      • UT Southwestern University Hospital- St. Paul
    • Dallas, Texas, United States, 75390
      • UT Southwestern University Hospital - Zale Lipshy
    • Fort Worth, Texas, United States, 76177-3204
      • US Oncology
    • The Woodlands, Texas, United States, 77380
      • US Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of locally advanced, unresectable or metastatic cutaneous or melanoma of unknown primary AJCC Stage IIIC or IV (uveal and mucosal melanoma are excluded)
• Presence of NRAS Q61 mutation in tumor tissue prior to randomization as determined by a Novartis designated central laboratory
• Naïve untreated patients or patients who have progressed on or after any number of prior lines of immunotherapy for unresectable locally advanced or metastatic melanoma
• Evidence of at least one measurable lesion as detected by radiological or photographic methods
• Adequate bone marrow, organ function, cardiac and laboratory parameters
• Normal functioning of daily living activities

Exclusion Criteria:

• Any untreated CNS metastases
• Uveal or mucosal melanoma
• History of or current evidence of retinal vein occlusion (RVO) or risk factors of RVO
• Patients with washout period < 6 weeks from the last dose of ipilimumab or other immunotherapy.
• Previous systemic chemotherapy for unresectable locally advanced or metastatic melanoma.
• History of Gilbert's syndrome
• Prior therapy with a MEK- inhibitor
• Impaired cardiovascular function or clinically significant cardiovascular diseases
• Uncontrolled arterial hypertension despite medical treatment
• HIV positive or active Hepatitis A or B
• Impairment of gastrointestinal function
• Patients who have undergone major surgery or radiotherapy ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure;
• Patients with neuromuscular disorders that are associated with elevated CK.
• Pregnant or nursing (lactating) women
• Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEK162	Drug: MEK162; MEK162 will be administered as a fixed dose of 45 mg (3 x 15 mg tablets) BID, with a glass of water and taken with or without food.
Active Comparator: Dacarbazine	Drug: Dacarbazine; Patients randomized to dacarbazine will receive an IV infusion of dacarbazine 1000 mg/m2 over the course of 1 hour on day 1 and then every three weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	PFS: time from randomization to first documented PD or death due to any cause, whichever occurred first. RECIST 1.1, PD: >=20% increase in sum of diameter of target lesions (TLs) taking as reference the smallest sum on study (including baseline sum), sum must also be an absolute increase of >=5 mm; unequivocal progression of existing non-TLs; appearance of >=1 lesion. Complete response (CR): disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs. Partial response (PR): >=30% decrease in sum of diameter of all TLs, referring baseline sum of diameters. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor increase in lesions qualified for PD referring smallest sum diameter. With no event at time of analysis cut-off or at start of any new anti-neoplastic therapy, PFS censored at date of last adequate tumor assessment of CR, PR or SD.	From the date of randomization to the date of the first documented PD or death, whichever occurred first (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a participant was not known to have died, overall survival was censored at the date of last known date participant alive.	From the date of randomization to the date of death (maximum up to 107 weeks for binimetinib arm; maximum up to 88 weeks for dacarbazine arm)
Overall Response Rate (ORR)	ORR: percentage of participants with best overall response (BOR) of CR or PR. BOR: best response recorded from start of treatment until CR or PR. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter of all TLs, taking as reference baseline sum of diameters. ORR is reported for confirmed and unconfirmed responses. Confirmed CR or PR = at least 2 determinations of CR or PR at least 4 weeks apart before PD. PD: >=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non TLs. Appearance of at least 1 new lesion.	From date of randomization until first documented response of CR or PR (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Time to Response (TTR)	TTR: time between date of randomization until first documented response of CR or PR. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter (dia) of all TLs, referring baseline sum of dia; c) PD: >=20% increase in sum of diameter of all measured TLs taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non-TLs. Appearance of >=1 new lesion. Participants who did not achieve PR or CR censored at last adequate tumor assessment date when they did not have PFS event (time from date of randomization to date of first documented PD or death due to any cause, whichever occur first) or at maximum follow-up when they had PFS event.	From date of randomization until first documented response of CR or PR (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Duration of Objective Response (DOR)	DOR: time from date of first documented response (CR or PR) to first documented progression or death due to underlying cancer. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter (dia) of all TLs, referring baseline sum of dia; c) PD: >=20% increase in sum of diameter of all measured target lesions taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non-target lesions. Appearance of at least 1 new lesion. If a participant with a CR or PR had no PD or death due to underlying cancer, participants was censored at date of last adequate tumor assessment.	From the date of first documented response (CR or PR) to the first documented progression or death (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Disease Control Rate (DCR)	DCR was calculated as the percentage of participants with a BOR of CR, PR, SD RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; c) SD: neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD taking as reference the smallest sum diameters; d) PD: >=20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non-target lesions. Appearance of at least 1 new lesion.	From date of randomization until first documented response of CR, PR, SD or non-CR/non-PD (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period. AEs included all SAEs and non-SAEs.	From baseline up to 219.4 weeks for binimetinib arm; From baseline up to 123.9 weeks for dacarbazine arm
Number of Participants With Clinically Notable Hematology Shifts Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03	Clinically notable shifts are defined as worsening by at least 2 grades or to >= grade 3. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Number of Participants With Clinically Notable Clinical Chemistry/Biochemistry Shifts Based on NCI-CTCAE Grade, Version 4.03	Clinically notable shifts are defined as worsening by at least 2 grades or to >= grade 3. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Number of Participants With Clinically Notable Vital Signs	Abnormalities criteria included: low/high pulse rate (beats per minute [bpm]):<=50bpm with decrease from baseline >=15bpm/>=120bpm with increase from baseline >=15bpm; Low/high systolic blood pressure (millimeters of mercury [mmHg]): <=90mmHg with decrease from baseline >=20mmHg/>=160mmHg with increase from baseline >=20mmHg; Low/high diastolic blood pressure [mmHg]: <=50mmHg with decrease from baseline >=15mmHg/>=100mmHg with increase from baseline >=15mmHg; Low/high body weight (kilogram [kg]): >=20% decrease from baseline / >=10% increase from baseline; Low/high body temperature (degree Celsius [°C]): <=36°C / >= 37.5°C	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Number of Participants With Notable Electrocardiogram (ECG) Values	Criteria for notable ECG values were as follow: QT interval (in millisecond [msec]) new (newly occurring post-baseline value) greater than (>) 450, 480, 500, increase from baseline >30, increase from baseline >60; corrected QT interval by Fredericia formula (QTcF) in msec new (newly occurring post-baseline value) > 450, 480, 500, increase from baseline >30, increase from baseline >60; corrected QT interval by Bazett's formula (QTcB) in msec new (newly occurring post-baseline value) > 450, 480, 500, increase from baseline >30, increase from baseline >60; heart rate in bpm new (newly occurring post-baseline value) <60 and >100.	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Number of Participants With Adverse Events of Special Interest: Cardiac Events	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Here, in this outcome measure data is reported for events falling in any of the grades.	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Number of Participants With Clinically Significant Findings in Physical Examination	A complete physical examination included the examination of general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and neurological systems. If indicated based on medical history and/or symptoms, rectal, external genitalia, breast, and pelvic examinations were performed. Clinical significance in physical examination was reported as adverse events.	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Number of Participants With Adverse Events of Special Interest: Ocular Events	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Grade 1: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL; Grade 3: Severe or medically significant but not immediately sight threatening; Hospitalization or prolongation of existing hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Sight-threatening consequences; urgent intervention indicated; blindness (20/200 or worse) in the affected eye. Here, in this outcome measure data is reported for events falling in any of the grades.	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Plasma Concentration of Binimetinib		Day 1 of Week 1: Pre-dose, 1, 1.5, 2, 10 hours post-dose; Day 1 of Weeks 4, 7: Pre-dose, 1.5 hours post-dose; Day 1 of Weeks 10, 13: Pre-dose
Time to Definitive 10% Deterioration in Global Health Status Score of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)	The time to definitive 10% deterioration was defined as the time from the date of randomization to the date of event, which was defined as death due to any cause or at least 10% worsening of the corresponding scale score, relative to baseline, with no later improvement above this threshold observed during the course of the study or death due to any cause. If a participant had no event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last adequate health related quality of life (HRQoL) evaluation. EORTC QLQ-C30: 5 functional scales (physical, role, cognitive, emotional, and social), a global health status scale, 3 symptom scales (nausea/vomiting, pain, fatigue) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All scales and single-item measures range =0 to 100. High score for global health status = high quality of life.	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm
Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Weeks 4, 7, 13, 19, 25, 34, 43, 52, 61, 70, End of Treatment, Safety Follow-up Visit, Post-Treatment Follow-up Visit 1, 2, 3, 4, 5 and 6	EORTC QLQ-C30: 5 functional scales (physical, role, cognitive, emotional, and social), a h global health status scale, 3 symptom scales (nausea/vomiting, pain, fatigue) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All scales and single-item measures range =0 to 100. High score for global health status = high quality of life. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.	Both arms: Baseline, Day 1 Treatment Week (TW) 4,7,13,19,25,34,43,52; Post-treatment follow-up Visit (FUV) 1 to 6; Binimetinib: Day 1 TW61,70; End of treatment (EOT= TW73); Safety FUV=30 days post TW73; Dacarbazine: EOT=TW 57;Safety FUV=30 days post TW57
Change From Baseline in EuroQoL-5 Dimensions- 5 Levels (EQ-5D-5L) Index Score at Weeks 4, 7, 13, 19, 25, 34, 43, 52, 61, 70, End of Treatment, Safety Follow-up Visit, Post-treatment Follow-up Visit 1, 2, 3, 4, 5 and 6	EQ-5D-5L, is a standardized measure of health utility that provides a single index value for one's health status. EQ-5D-5L contained 1 item for each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Index score: participant responses to the 5 dimensions reflected a specific health state that corresponded to a population preference weight for that state on a continuous scale of 0 (death) to 1 (perfect health). Higher index scores = better health state. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.	Both arms: Baseline, Day 1 Treatment Week (TW) 4,7,13,19,25,34,43,52; Post-treatment follow-up Visit (FUV) 1 to 6; Binimetinib: Day 1 TW61,70; End of treatment (EOT= TW73); Safety FUV=30 days post TW73; Dacarbazine: EOT=TW 57;Safety FUV=30 days post TW57
Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)	ECOG PS was used to assess the physical health of participants, and ranged from 0 (most active) to 5 (dead). ECOG PS grades: 0= fully active, able to carry on all pre-disease performance without restriction, 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 2= ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours, 3= capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4=completely disabled. cannot carry on any selfcare. Totally confined to bed or chair and 5= dead. Definitive deterioration is defined as on treatment death due to any cause or decrease in ECOG PS by at least one category from baseline score.	From baseline up to 73 weeks 3 days for binimetinib arm; From baseline up to 57 weeks 3 days for dacarbazine arm
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)	ECOG PS was used to assess the physical health of participants, and ranged from 0 (most active) to 5 (dead). ECOG PS grades: 0= fully active, able to carry on all pre-disease performance without restriction, 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 2= ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours, 3= capable of only limited self-care, 4=completely disabled. cannot carry on any selfcare. Totally confined to bed or chair confined to bed or chair more than 50% of waking hours and 5= dead. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.	For both arms: Baseline, Weeks 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55 and 30-day Follow-up For binimetinib only: Weeks 58, 61, 64, 67, 70, 73
Number of Participants With Neuroblastoma RAS Viral (V-ras) Oncogene Homolog (NRAS) Mutation Status at Baseline	Number of participants with NRAS mutation status at baseline were reported.	Baseline

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozon V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):435-445. doi: 10.1016/S1470-2045(17)30180-8. Epub 2017 Mar 9.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): June 4, 2019

Study Registration Dates

• First Submitted: January 4, 2013
• First Submitted That Met QC Criteria: January 4, 2013
• First Posted (Estimate): January 8, 2013

Study Record Updates

• Last Update Posted (Actual): March 22, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Melanoma; Skin cancer; Neoplasm Metastasis; Skin Neoplasms; Skin disease; Cutaneous melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Dacarbazine
• Other Study ID Numbers: CMEK162A2301; C4211002 (Other Identifier: Alias Study Number); 2012-003593-51 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.