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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Array BioPharma
ClinicalTrials.gov Identifier:
NCT01763164
First received: January 4, 2013
Last updated: July 13, 2016
Last verified: July 2016
  Purpose
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

Condition Intervention Phase
Metastatic or Unresectable Cutaneous Melanoma
Drug: MEK162
Drug: Dacarbazine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Array BioPharma:

Primary Outcome Measures:
  • Progression free survival (PFS) [ Time Frame: The final PFS analysis is expected approximately 26 months after FPFV. ] [ Designated as safety issue: No ]
    PFS is defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever occurs first. PFS will be determined by a Blinded Independent Review Committee (BIRC). The local Investigator's assessments will be used as supportive analyses.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Final analysis is expected to occur 31 months after FPFV ] [ Designated as safety issue: No ]
    To compare OS between treatment arms. OS is calculated as the time from date of randomization to date of death due to any cause.

  • Overall Response Rate (ORR) [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: No ]
    ORR calculated as the proportion of patient with a best overall response of complete response (CR) or partial response (PR). ORR will be calculated for confirmed and unconfirmed responses separately.

  • Time to Objective Response (TTR) [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: No ]
    TTR calculated as the time from date of randomization until first documented complete response (CR) or partial response(PR).

  • Duration of objective response (DOR) [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: No ]
    DOR calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer

  • Disease control rate (DCR) [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: No ]
    DCR calculated as the proportion of patient with a best overall response of CR, PR or stable disease (SD)

  • Number of patients with adverse events [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of MEK162 in this patient, changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), MUGA(Multi Gated Acquisition Scan)/echocardiogram and assessment of physical and ocular examinations graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03

  • Number of patients with serious adverse events [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of MEK162 in this patient, changes in hematology and chemistry values, vital signs, ECGs, MUGA/echocardiogram and assessment of physical and ocular examinations graded according to the NCI CTCAE v4.03

  • Time to definitive 10% deterioration in the global health status score of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatments.

  • Change from baseline in the global health status score of the EORTC QLQ-C30 [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatment.

  • Change from baseline in the EQ-5D-5L (EuroQol Group standardised instrument for use as a measure of health outcome) [ Time Frame: Approximately 26 months after the FPFV ] [ Designated as safety issue: No ]
    To compare the global health status between the treatment.


Enrollment: 402
Study Start Date: July 2013
Estimated Study Completion Date: March 2017
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763164

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Locations
United States, Arkansas
Highlands Oncology Group SC
Fayetteville, Arkansas, United States, 72703
United States, Florida
Florida Cancer Specialists Dept of Oncology (2)
Fort Myers, Florida, United States, 33901
Florida Cancer Specialists SC
Fort Myers, Florida, United States, 33901
United States, Illinois
Oncology Specialists, SC SC - 5
Park Ridge, Illinois, United States, 60068-0736
United States, Indiana
Indiana University Health Goshen Center for Cancer SC
Goshen, Indiana, United States, 46526
United States, Maine
Eastern Maine Medical Center Research Center SC
Bangor, Maine, United States, 04401
United States, Maryland
Weinberg Cancer Institute at Franklin Square Hospital Dept of Oncology
Baltimore, Maryland, United States, 21237-3998
United States, Massachusetts
Massachusetts General Hospital SC -6
Boston, Massachusetts, United States, 02114
United States, Michigan
Karmanos Cancer Institute SC - 1
Detroit, Michigan, United States, 48201
United States, Minnesota
Minnesota Oncology Hematology, P.A. Fridley Location
Minneapolis, Minnesota, United States, 55404
United States, Nebraska
Nebraska Methodist Hospital Estabrook Cancer Center
Omaha, Nebraska, United States, 68114
United States, New Jersey
Cooper Cancer Center SC
Camden, New Jersey, United States, 08103
Hackensack University Medical Center SC-2
Hackensack, New Jersey, United States, 07601
United States, Ohio
Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State University
Columbus, Ohio, United States, 43210
United States, Oregon
Northwest Cancer Specialists Compass Oncology - SC
Portland, Oregon, United States, 97210
Kaiser Permanente Northwest Dept of Kaiser Northwest (3)
Portland, Oregon, United States, 97227
Oregon Health & Science University SC-7
Portland, Oregon, United States, 97239
United States, Pennsylvania
St. Luke's Hospital and Health Network SC
Bethlehem, Pennsylvania, United States
Penn State University / Milton S. Hershey Medical Center SC-2
Hershey, Pennsylvania, United States, 17033-0850
Thomas Jefferson University Hospital SC
Philadelphia, Pennsylvania, United States, 19107-5098
United States, Tennessee
Sarah Cannon Research Institute SC - 2
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology, P.A. SC
Austin, Texas, United States, 78121
Baylor Health Care System/Sammons Cancer Center Oncology
Dallas, Texas, United States, 75246
University of Texas Southwestern Medical Center SC (5)
Dallas, Texas, United States, 75390-8527
Argentina
Novartis Investigative Site
Rosario, Santa Fe, Argentina, S2000KZE
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Rio Negro, Viedma, Argentina, 8500
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Buenos Aires, Argentina, C1050AAK
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Buenos Aires, Argentina, C1426ANZ
Australia, New South Wales
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Camperdown, New South Wales, Australia, 2050
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Gateshead, New South Wales, Australia, 2290
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North Sydney, New South Wales, Australia, 2060
Australia, Queensland
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Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
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Adelaide, South Australia, Australia, 5000
Austria
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Innsbruck, Tyrol, Austria, 6020
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Graz, Austria, 8036
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Salzburg, Austria, 5020
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Wien, Austria, A-1090
Belgium
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Leuven, Belgium, 3000
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Liege, Belgium, 4000
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Wilrijk, Belgium, 2610
Brazil
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Rio de Janeiro, RJ, Brazil, 20220410
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Passo Fundo, RS, Brazil, 99010-260
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Porto Alegre, RS, Brazil, 90035-903
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Sao Paulo, SP, Brazil, 01321-001
Canada, Alberta
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Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
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London, Ontario, Canada, N6A 4L6
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Toronto, Ontario, Canada, M4N 3M5
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Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
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Montreal, Quebec, Canada, H3T 1E2
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Sainte-Foy, Quebec, Canada, G1V 4T3
Czech Republic
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Brno, Czech Republic, 65653
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Ostrava Poruba, Czech Republic, 708 52
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Praha 10, Czech Republic, 100 34
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Praha 2, Czech Republic, 128 08
France
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Paris, Cedex 10, France, 75475
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Angers, France, 49033
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Bordeaux Cedex, France, 33075
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Boulogne Billancourt, France, 92104
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Le Mans Cedex 09, France, 72037
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LILLE Cedex, France, 59037
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Lyon Cedex, France, 69373
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Marseille Cedex 05, France, 13885
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Nice Cedex 3, France, 06202
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Pierre-Benite Cedex, France, 69495
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Reims, France, 51092
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Rouen Cedex, France, 76031
Germany
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Mannheim, Baden-Württemberg, Germany, 68305
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Berlin, Germany, 10098
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Dresden, Germany, 01307
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Erfurt, Germany, 99089
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Essen, Germany, 45147
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Frankfurt, Germany, 60590
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Freiburg, Germany, 79106
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Gera, Germany, 07548
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Hannover, Germany, 30625
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Heidelberg, Germany, 69120
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Kiel, Germany, 24105
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Köln, Germany, 50937
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Leipzig, Germany, 04103
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Lübeck, Germany, 23538
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Minden, Germany, 32429
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Muenchen, Germany, 80336
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Muenster, Germany, 48157
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Nuernberg, Germany, 90419
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Quedlinburg, Germany, 06484
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Regensburg, Germany, 93053
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Stade, Germany, 21682
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Tübingen, Germany, 72076
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Ulm, Germany, 89081
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Würzburg, Germany, 97080
Greece
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Athens, GR, Greece, 115 27
Hungary
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Budapest, Hungary, 1134
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Budapest, Hungary, H-1122
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Kaposvar, Hungary, 7400
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Szolnok, Hungary, H-5000
Israel
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Haifa, Israel, 31096
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Jerusalem, Israel, 9112001
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Ramat Gan, Israel, 5266202
Italy
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Bari, BA, Italy, 70126
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Bergamo, BG, Italy, 24128
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Brescia, BS, Italy, 25123
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Genova, GE, Italy, 16132
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Milano, MI, Italy, 20133
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Padova, PD, Italy, 35100
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Roma, RM, Italy, 00128
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Roma, RM, Italy, 00167
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Siena, SI, Italy, 53100
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Torino, TO, Italy, 10126
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Napoli, Italy, 80131
Japan
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Fukuoka-city, Fukuoka, Japan, 812-8582
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Matsumoto, Nagano, Japan, 390-8621
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Hirakata-city, Osaka, Japan, 573-1191
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Chuo-ku, Tokyo, Japan, 104-0045
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 03722
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Seoul, Korea, Korea, Republic of, 05505
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Seoul, Korea, Korea, Republic of, 06351
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Seoul, Korea, Korea, Republic of, 110 744
Netherlands
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Amsterdam, Netherlands, 1066 CX
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Leiden, Netherlands, 2300 RC
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Nijmegen, Netherlands, 6525 GA
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Zwolle, Netherlands, 8025 AB
Poland
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Warszawa, Poland, 02-781
Portugal
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Almada, Portugal, 2801-951
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Lisboa, Portugal, 1099 - 023
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Lisboa, Portugal, 1649-035
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Porto, Portugal, 4200-072
Russian Federation
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Ryazan, Russia, Russian Federation, 390011
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Moscow, Russian Federation, 115478
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St. Petersburg, Russian Federation, 197758
Slovakia
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Bratislava, Slovak Republic, Slovakia, 83310
South Africa
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Bloemfontein, South Africa, 9301
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Johannesburg, South Africa, 2199
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Pretoria, South Africa, 0002
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Pretoria, South Africa, 0027
Spain
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Malaga, Andalucia, Spain, 29010
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Sevilla, Andalucia, Spain, 41009
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Toledo, Castilla la Mancha, Spain, 45004
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Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46009
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46014
Novartis Investigative Site
Badajoz, Extremadura, Spain, 06080
Novartis Investigative Site
La Coruna, Galicia, Spain, 15006
Novartis Investigative Site
Las Palmas de Gran Canarias, Las Palmas de Gran Canaria, Spain, 35016
Novartis Investigative Site
Pamplona, Navarra, Spain, 31008
Novartis Investigative Site
Madrid, Spain, 28007
Novartis Investigative Site
Madrid, Spain, 28033
Novartis Investigative Site
Madrid, Spain, 28040
Novartis Investigative Site
Madrid, Spain, 28050
Sweden
Novartis Investigative Site
Lund, Sweden, SE-221 85
Switzerland
Novartis Investigative Site
Genève, Switzerland, 1211
Novartis Investigative Site
Lausanne, Switzerland, 1011
Novartis Investigative Site
Zürich, Switzerland, 8091
Turkey
Novartis Investigative Site
Ankara, Turkey, 06490
Novartis Investigative Site
Istanbul, Turkey, 34303
Novartis Investigative Site
Izmir, Turkey, 35040
United Kingdom
Novartis Investigative Site
Bristol, Avon, United Kingdom, BS2 8ED
Novartis Investigative Site
Truro, Cornwall, United Kingdom, TR1 3LJ
Novartis Investigative Site
Surrey, England, United Kingdom, GU2 7XX
Novartis Investigative Site
Birmingham, Surrey, United Kingdom, B15 2TH
Novartis Investigative Site
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Novartis Investigative Site
Chelmsford, United Kingdom, CM1 7ET
Novartis Investigative Site
London, United Kingdom, SW3 6JJ
Novartis Investigative Site
Merseyside, United Kingdom, L63 4JY
Novartis Investigative Site
Preston, United Kingdom, PR2 9HT
Novartis Investigative Site
Swansea, United Kingdom, SA2 8QA
Sponsors and Collaborators
Array BioPharma
Investigators
Study Director: Array BioPharma 303-381-6604
  More Information

Responsible Party: Array BioPharma
ClinicalTrials.gov Identifier: NCT01763164     History of Changes
Other Study ID Numbers: CMEK162A2301  2012-003593-51 
Study First Received: January 4, 2013
Last Updated: July 13, 2016
Health Authority: United States: Food and Drug Administration
Australia: National Health and Medical Research Council
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Italy: The Italian Medicines Agency
Argentina: Ministry of Health
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Hungary: Institutional Ethics Committee
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Turkey: Ministry of Health
Brazil: Ministry of Health
Greece: Ministry of Health and Welfare

Keywords provided by Array BioPharma:
Melanoma
Cutaneous melanoma
Skin disease
Skin cancer
Skin Neoplasms
Neoplasm Metastasis

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on September 28, 2016