ClinicalTrials.gov
ClinicalTrials.gov Menu

Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma (COMBI-v)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01597908
Recruitment Status : Active, not recruiting
First Posted : May 14, 2012
Results First Posted : December 4, 2014
Last Update Posted : April 27, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 694 subjects will be randomised 1:1 (combination therapy:vemurafenib). The primary endpoint is overall survival (OS) for subjects receiving the combination therapy compared with those receiving vemurafenib.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Dabrafenib Drug: Vemurafenib Drug: Trametinib Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 704 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Randomised, Open-label Study Comparing the Combination of the BRAF Inhibitor, Dabrafenib and the MEK Inhibitor, Trametinib to the BRAF Inhibitor Vemurafenib in Subjects With Unresectable (Stage IIIc) or Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma
Actual Study Start Date : June 4, 2012
Actual Primary Completion Date : April 17, 2014
Estimated Study Completion Date : March 18, 2019


Arm Intervention/treatment
Experimental: Dabrafenib plus Trametinib
BRAF inhibitor plus MEK inhibitor
Drug: Dabrafenib
dabrafenib 150 mg twice daily po
Drug: Trametinib
trametinib 2 mg once daily po
Active Comparator: Vemurafenib
BRAF inhibitor
Drug: Vemurafenib
vemurafenib 960 mg twice daily po



Primary Outcome Measures :
  1. Overall Survival [ Time Frame: From randomization until death due to any cause (up to Study Week 92) ]
    Overall survival is defined as the time from randomization until death due to any cause.


Secondary Outcome Measures :
  1. Progression-free Survival, as Assessed by the Investigator [ Time Frame: From randomization to the first documented occurrence of disease progression or death due to any cause (up to Study Week 80) ]
    Progression-free survival (PFS) is defined as the time from randomization to the first documented occurrence of disease progression or death due to any cause. PFS for investigator-assessed response was summarized per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, which is a set of published rules defining when cancer patients 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.

  2. Overall Response, as Assessed by the Investigator [ Time Frame: Screening, Week 8 and every 8 weeks thereafter through Week 56, and then every 12 weeks ]
    Overall response is defined as the number of responders (complete response [CR] + partial response [PR] per RECIST, Version 1.1) as summarized by Investigator assessment. CR is defined as the disappearance of all evidence of target lesions. PR is defined as at least a 30% reduction from Baseline in the sum of the longest diameter (LD) of all target lesions. Data are reported as those participants with measureable disease.

  3. Duration of Response, as Assessed by the Investigator [ Time Frame: From the first documented evidence of a CR or PR until the earliest date of disease progression or death due to any cause (up to Study Week 80) ]
    Duration of response is defined as the time from the first documented evidence of a CR (disappearance of all evidence of target lesions) or a PR (at least a 30% reduction from Baseline in the sum of the longest diameter of all target lesions) until disease progression 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 at least1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. Data are summarized per RECIST, Version 1.1.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • >= 18 years of age
  • Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
  • Measurable disease according to RECIST 1.1
  • Women of childbearing potential with negative serum pregnancy test prior to randomisation
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Adequate baseline organ function

Exclusion Criteria:

  • Any prior use of a BRAF or MEK inhibitor
  • Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
  • History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer)
  • Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed)
  • Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation
  • History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy)
  • History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01597908


  Hide Study Locations
Locations
United States, Alabama
Novartis Investigative Site
Birmingham, Alabama, United States, 35243
United States, Arizona
Novartis Investigative Site
Gilbert, Arizona, United States, 85234
United States, California
Novartis Investigative Site
Beverly Hills, California, United States, 90211
Novartis Investigative Site
San Francisco, California, United States, 94115
Novartis Investigative Site
Vallejo, California, United States, 94589
United States, Colorado
Novartis Investigative Site
Aurora, Colorado, United States, 80010
United States, Florida
Novartis Investigative Site
Jacksonville, Florida, United States, 32204
Novartis Investigative Site
Miami Beach, Florida, United States, 33140
Novartis Investigative Site
Orlando, Florida, United States, 32804
United States, Georgia
Novartis Investigative Site
Atlanta, Georgia, United States, 30322
Novartis Investigative Site
Atlanta, Georgia, United States, 30341
United States, Iowa
Novartis Investigative Site
Iowa City, Iowa, United States, 52242
United States, Michigan
Novartis Investigative Site
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Novartis Investigative Site
Fridley, Minnesota, United States, 55432
United States, Missouri
Novartis Investigative Site
Saint Louis, Missouri, United States, 63110
United States, Nevada
Novartis Investigative Site
Las Vegas, Nevada, United States, 89148
United States, New Jersey
Novartis Investigative Site
Hackensack, New Jersey, United States, 07601
Novartis Investigative Site
New Brunswick, New Jersey, United States, 08901
United States, New York
Novartis Investigative Site
New York, New York, United States, 10029
United States, North Carolina
Novartis Investigative Site
Chapel Hill, North Carolina, United States, 27599-7600
Novartis Investigative Site
Charlotte, North Carolina, United States, 28204
Novartis Investigative Site
Durham, North Carolina, United States, 27710
United States, Ohio
Novartis Investigative Site
Cincinnati, Ohio, United States, 45219
Novartis Investigative Site
Columbus, Ohio, United States, 43210
United States, Oregon
Novartis Investigative Site
Bend, Oregon, United States, 97701
Novartis Investigative Site
Portland, Oregon, United States, 97213
Novartis Investigative Site
Portland, Oregon, United States, 97239
United States, South Carolina
Novartis Investigative Site
Charleston, South Carolina, United States, 29425
Novartis Investigative Site
Greenville, South Carolina, United States, 29605
United States, Tennessee
Novartis Investigative Site
Nashville, Tennessee, United States, 37232
United States, Texas
Novartis Investigative Site
Dallas, Texas, United States, 75246
United States, Utah
Novartis Investigative Site
Salt Lake City, Utah, United States, 84106
Novartis Investigative Site
Salt Lake City, Utah, United States, 84112-5550
United States, Vermont
Novartis Investigative Site
Burlington, Vermont, United States, 05403
United States, Virginia
Novartis Investigative Site
Charlottesville, Virginia, United States, 22903
United States, Wisconsin
Novartis Investigative Site
Milwaukee, Wisconsin, United States, 53226
Argentina
Novartis Investigative Site
Capital Federal, Buenos Aires, Argentina, C1426ANZ
Novartis Investigative Site
Viedma, Río Negro, Argentina, R8500ACE
Novartis Investigative Site
Rosario, Santa Fe, Argentina, S2000KZE
Novartis Investigative Site
Ciudad Autonoma de Buenos Aires, Argentina, C1121ABE
Novartis Investigative Site
San Miguel de Tucuman, Argentina, T4000IAK
Novartis Investigative Site
Santa Fe, Argentina, 3000
Australia, New South Wales
Novartis Investigative Site
North Sydney, New South Wales, Australia, 2060
Novartis Investigative Site
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Novartis Investigative Site
Greenslopes, Queensland, Australia, 4120
Novartis Investigative Site
Herston, Queensland, Australia, 4029
Novartis Investigative Site
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Novartis Investigative Site
Woodville, South Australia, Australia, 5011
Australia, Victoria
Novartis Investigative Site
Box Hill, Victoria, Australia, 3128
Novartis Investigative Site
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
Novartis Investigative Site
Nedlands, Western Australia, Australia, 6009
Austria
Novartis Investigative Site
Graz, Austria, A-8036
Novartis Investigative Site
Innsbruck, Austria, 6020
Novartis Investigative Site
Salzburg, Austria, A-5020
Novartis Investigative Site
Wien, Austria, 1090
Novartis Investigative Site
Wien, Austria, A-1030
Belgium
Novartis Investigative Site
Brasschaat, Belgium, 2930
Novartis Investigative Site
Brussels, Belgium, 1200
Novartis Investigative Site
Brussel, Belgium, 1090
Novartis Investigative Site
Gent, Belgium, 9000
Novartis Investigative Site
Kortrijk, Belgium, 8500
Novartis Investigative Site
Leuven, Belgium, 3000
Novartis Investigative Site
Namur, Belgium, 5000
Novartis Investigative Site
Wilrijk, Belgium, 2610
Brazil
Novartis Investigative Site
Ijui, Rio Grande Do Sul, Brazil, 98700-000
Novartis Investigative Site
Itajai, Santa Catarina, Brazil, 88301-215
Novartis Investigative Site
Sao Paulo - SP, Brazil, 01323-900
Canada, Alberta
Novartis Investigative Site
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
Novartis Investigative Site
Kelowna, British Columbia, Canada, V1Y 5L3
Novartis Investigative Site
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
Novartis Investigative Site
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
Novartis Investigative Site
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Novartis Investigative Site
Kingston, Ontario, Canada, K7L 5P9
Novartis Investigative Site
Oshawa, Ontario, Canada, L1G 2B9
Novartis Investigative Site
Ottawa, Ontario, Canada, K1H 8L6
Novartis Investigative Site
Toronto, Ontario, Canada, M4N 3M5
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H2L 4M1
Canada
Novartis Investigative Site
Quebec, Canada, G1R 2J6
Czechia
Novartis Investigative Site
Olomouc, Czechia, 775 20
Novartis Investigative Site
Ostrava, Czechia, 708 52
Novartis Investigative Site
Praha 10, Czechia, 100 34
Novartis Investigative Site
Praha 2, Czechia, 128 08
Novartis Investigative Site
Zlin, Czechia, 76275
Denmark
Novartis Investigative Site
Arhus C, Denmark, 8000
Novartis Investigative Site
Herlev, Denmark, 2730
Novartis Investigative Site
Odense, Denmark, 5000 C
Finland
Novartis Investigative Site
Helsinki, Finland, 00029
Novartis Investigative Site
Jyvaskyla, Finland, 40620
Novartis Investigative Site
Tampere, Finland, 33520
Novartis Investigative Site
Turku, Finland, 20520
France
Novartis Investigative Site
Bordeaux, France, 33075
Novartis Investigative Site
Grenoble, France, 38043
Novartis Investigative Site
Lille, France, 59037
Novartis Investigative Site
Marseille cedex 5, France, 13385
Novartis Investigative Site
Montpellier cedex 5, France, 34295
Novartis Investigative Site
Nantes, France, 44093
Novartis Investigative Site
Nice, France, 06202
Novartis Investigative Site
Paris Cedex 10, France, 75475
Novartis Investigative Site
Reims Cedex, France, 51092
Novartis Investigative Site
Rennes Cedex, France, 35042
Novartis Investigative Site
Villejuif cedex, France, 94805
Germany
Novartis Investigative Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
Novartis Investigative Site
Heilbronn, Baden-Wuerttemberg, Germany, 74078
Novartis Investigative Site
Mannheim, Baden-Wuerttemberg, Germany, 68167
Novartis Investigative Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
Novartis Investigative Site
Erlangen, Bayern, Germany, 91054
Novartis Investigative Site
Muenchen, Bayern, Germany, 80337
Novartis Investigative Site
Muenchen, Bayern, Germany, 80802
Novartis Investigative Site
Muenchen, Bayern, Germany, 80804
Novartis Investigative Site
Nuernberg, Bayern, Germany, 90419
Novartis Investigative Site
Regensburg, Bayern, Germany, 93053
Novartis Investigative Site
Wuerzburg, Bayern, Germany, 97080
Novartis Investigative Site
Buxtehude, Niedersachsen, Germany, 21614
Novartis Investigative Site
Hannover, Niedersachsen, Germany, 30625
Novartis Investigative Site
Bonn, Nordrhein-Westfalen, Germany, 53127
Novartis Investigative Site
Essen, Nordrhein-Westfalen, Germany, 45122
Novartis Investigative Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Novartis Investigative Site
Ludwigshafen, Rheinland-Pfalz, Germany, 67063
Novartis Investigative Site
Mainz, Rheinland-Pfalz, Germany, 55131
Novartis Investigative Site
Magdeburg, Sachsen-Anhalt, Germany, 39120
Novartis Investigative Site
Dresden, Sachsen, Germany, 01307
Novartis Investigative Site
Leipzig, Sachsen, Germany, 04103
Novartis Investigative Site
Kiel, Schleswig-Holstein, Germany, 24105
Novartis Investigative Site
Luebeck, Schleswig-Holstein, Germany, 23538
Novartis Investigative Site
Erfurt, Thueringen, Germany, 99089
Novartis Investigative Site
Gera, Thueringen, Germany, 07548
Hungary
Novartis Investigative Site
Budapest, Hungary, 1062
Novartis Investigative Site
Budapest, Hungary, H-1122
Novartis Investigative Site
Debrecen, Hungary, 4032
Novartis Investigative Site
Gyor, Hungary, H-9024
Novartis Investigative Site
Kaposvar, Hungary, 7400
Novartis Investigative Site
Miskolc, Hungary, 3526
Novartis Investigative Site
Szeged, Hungary, 6720
Ireland
Novartis Investigative Site
Co.Cork, Ireland
Novartis Investigative Site
Dublin, Ireland, 4
Novartis Investigative Site
Dublin, Ireland, 7
Novartis Investigative Site
Dublin, Ireland, 9
Novartis Investigative Site
Galway, Ireland
Israel
Novartis Investigative Site
Jerusalem, Israel
Novartis Investigative Site
Ramat Gan, Israel, 52621
Italy
Novartis Investigative Site
Napoli, Campania, Italy, 80131
Novartis Investigative Site
Roma, Lazio, Italy, 00167
Novartis Investigative Site
Genova, Liguria, Italy, 16132
Novartis Investigative Site
Bergamo, Lombardia, Italy, 24128
Novartis Investigative Site
Milano, Lombardia, Italy, 20133
Novartis Investigative Site
Milano, Lombardia, Italy, 20141
Novartis Investigative Site
Pisa, Toscana, Italy, 56126
Novartis Investigative Site
Padova, Veneto, Italy, 35128
Korea, Republic of
Novartis Investigative Site
Goyang-si, Gyeonggi-Do, Korea, Republic of, 410-769
Novartis Investigative Site
Seoul, Korea, Republic of, 03080
Novartis Investigative Site
Seoul, Korea, Republic of, 135-710
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site
Amsterdam, Netherlands, 1081 HV
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Novartis Investigative Site
Leeuwarden, Netherlands, 8934 AD
Novartis Investigative Site
Leiden, Netherlands, 2333 ZA
Novartis Investigative Site
Rotterdam, Netherlands, 3075 EA
New Zealand
Novartis Investigative Site
Christchurch, New Zealand, 8011
Novartis Investigative Site
Newtown, Wellington, New Zealand, 6002
Norway
Novartis Investigative Site
Kristiansand, Norway, 4604
Novartis Investigative Site
Lorenskog, Norway, 1478
Novartis Investigative Site
Oslo, Norway, 0310
Poland
Novartis Investigative Site
Gdansk, Poland, 80-215
Novartis Investigative Site
Konin, Poland, 62-500
Novartis Investigative Site
Poznan, Poland, 60-693
Novartis Investigative Site
Warszawa, Poland, 02-781
Russian Federation
Novartis Investigative Site
Chelyabinsk, Russian Federation, 454087
Novartis Investigative Site
Magnitogorsk, Russian Federation, 455001
Novartis Investigative Site
Moscow, Russian Federation, 115478
Novartis Investigative Site
Moscow, Russian Federation, 143423
Novartis Investigative Site
Nizhniy Novgorod, Russian Federation, 603081
Novartis Investigative Site
Ryazan, Russian Federation, 390011
Novartis Investigative Site
St. Petersburg, Russian Federation, 197758
Spain
Novartis Investigative Site
Barcelona, Spain, 08036
Novartis Investigative Site
Hospitalet de Llobregat, Barcelona, Spain, 08907
Novartis Investigative Site
Las Palmas De Gran Canaria, Spain, 35016
Novartis Investigative Site
Madrid, Spain, 28007
Novartis Investigative Site
Madrid, Spain, 28050
Novartis Investigative Site
Palma de Mallorca, Spain, 07010
Novartis Investigative Site
Pamplona, Spain, 31008
Novartis Investigative Site
Valencia, Spain, 46009
Novartis Investigative Site
Valencia, Spain, 46014
Sweden
Novartis Investigative Site
Linkoping, Sweden, SE-581 85
Novartis Investigative Site
Umea, Sweden, SE-901 85
Switzerland
Novartis Investigative Site
Basel, Switzerland, 4031
Novartis Investigative Site
Lausanne, Switzerland, 1011
Novartis Investigative Site
Zurich, Switzerland, 8091
Taiwan
Novartis Investigative Site
Tainan, Taiwan, 704
Novartis Investigative Site
Taipei, Taiwan, 100
Novartis Investigative Site
Taoyuan, Taiwan, 333
Ukraine
Novartis Investigative Site
Dnipropetrovsk, Ukraine, 49102
Novartis Investigative Site
Donetsk, Ukraine, 83092
Novartis Investigative Site
Kharkiv, Ukraine, 61070
Novartis Investigative Site
Kyiv, Ukraine, 03022
Novartis Investigative Site
Lviv, Ukraine, 79031
Novartis Investigative Site
Sumy, Ukraine, 40005
Novartis Investigative Site
Uzhgorod, Ukraine, 88017
United Kingdom
Novartis Investigative Site
Cambridge, United Kingdom, CB2 0QQ
Novartis Investigative Site
Glasgow, United Kingdom, G12 0YN
Novartis Investigative Site
London, United Kingdom, NW3 2QG
Novartis Investigative Site
London, United Kingdom, SE1 7EH
Novartis Investigative Site
Manchester, United Kingdom, M20 4BX
Novartis Investigative Site
Southampton, United Kingdom, SO16 6YD
Novartis Investigative Site
Swansea, United Kingdom, SA2 8QA
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01597908     History of Changes
Other Study ID Numbers: 116513
First Posted: May 14, 2012    Key Record Dates
Results First Posted: December 4, 2014
Last Update Posted: April 27, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
BRAF inhibitor
Metastatic Melanoma
Cancer
MEK inhibitor

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
Trametinib
Vemurafenib
Dabrafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action