Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma
COMBI-v
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
3 other identifiers
interventional
704
27 countries
196
Brief Summary
This was a two-arm, open-label, randomized, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy with vemurafenib.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2012
Longer than P75 for phase_3
196 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 10, 2012
CompletedFirst Posted
Study publicly available on registry
May 14, 2012
CompletedStudy Start
First participant enrolled
June 4, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 17, 2014
CompletedResults Posted
Study results publicly available
December 4, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
April 25, 2019
CompletedFebruary 24, 2021
February 1, 2021
1.9 years
May 10, 2012
December 1, 2014
February 8, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
Overall Survival (OS) was defined as the interval of time between the date of randomization and the date of death due to any cause. For patients who did not die, OS was censored at the date of last contact.
From the date of randomization until date of death due to any cause (up to approximately 6 years)
Secondary Outcomes (3)
Progression-Free Survival (PFS), as Assessed by the Investigator
From randomization until the earliest date of disease progression (PD) or death due to any cause (up to approximately 6 years)
Overall Response Rate (ORR) During Randomized Phase, as Assessed by the Investigator
From randomization until the first documented complete response or partial response (up to approximately 6 years)
Duration of Response (DOR), as Assessed by the Investigator
From the time of the first documented response (CR or PR) until disease progression (up to approximately 6 years)
Study Arms (2)
Dabrafenib plus Trametinib
EXPERIMENTALBRAF inhibitor plus MEK inhibitor
Vemurafenib
ACTIVE COMPARATORBRAF inhibitor
Interventions
Dabrafenib 150 mg twice daily orally
Eligibility Criteria
You may qualify if:
- \>= 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (205)
Novartis Investigative Site
Birmingham, Alabama, 35243, United States
Novartis Investigative Site
Gilbert, Arizona, 85234, United States
Novartis Investigative Site
Beverly Hills, California, 90211, United States
Novartis Investigative Site
San Francisco, California, 94115, United States
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Vallejo, California, 94589, United States
Novartis Investigative Site
Aurora, Colorado, 80010, United States
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Jacksonville, Florida, 32204, United States
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Miami Beach, Florida, 33140, United States
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Orlando, Florida, 32804, United States
Novartis Investigative Site
Atlanta, Georgia, 30322, United States
Novartis Investigative Site
Atlanta, Georgia, 30341, United States
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Iowa City, Iowa, 52242, United States
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Ann Arbor, Michigan, 48109, United States
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Fridley, Minnesota, 55432, United States
Novartis Investigative Site
St Louis, Missouri, 63110, United States
Novartis Investigative Site
Las Vegas, Nevada, 89148, United States
Novartis Investigative Site
Hackensack, New Jersey, 07601, United States
Novartis Investigative Site
New Brunswick, New Jersey, 08901, United States
Novartis Investigative Site
New York, New York, 10029, United States
Novartis Investigative Site
Chapel Hill, North Carolina, 27599-7600, United States
Novartis Investigative Site
Charlotte, North Carolina, 28204, United States
Novartis Investigative Site
Durham, North Carolina, 27710, United States
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Cincinnati, Ohio, 45219, United States
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Columbus, Ohio, 43210, United States
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Bend, Oregon, 97701, United States
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Portland, Oregon, 97213, United States
Novartis Investigative Site
Portland, Oregon, 97239, United States
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Charleston, South Carolina, 29425, United States
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Greenville, South Carolina, 29605, United States
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Nashville, Tennessee, 37232, United States
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Dallas, Texas, 75246, United States
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Salt Lake City, Utah, 84106, United States
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Salt Lake City, Utah, 84112-5550, United States
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Burlington, Vermont, 05403, United States
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Charlottesville, Virginia, 22903, United States
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Milwaukee, Wisconsin, 53226, United States
Novartis Investigative Site
Capital Federal, Buenos Aires, C1426ANZ, Argentina
Novartis Investigative Site
Viedma, Río Negro Province, R8500ACE, Argentina
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Rosario, Santa Fe Province, S2000KZE, Argentina
Novartis Investigative Site
Buenos Aires, C1121ABE, Argentina
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San Miguel de Tucumán, T4000IAK, Argentina
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Santa Fe, 3000, Argentina
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North Sydney, New South Wales, 2060, Australia
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Westmead, New South Wales, 2145, Australia
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Greenslopes, Queensland, 4120, Australia
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Herston, Queensland, 4029, Australia
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South Brisbane, Queensland, 4101, Australia
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Woodville, South Australia, 5011, Australia
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Box Hill, Victoria, 3128, Australia
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Melbourne, Victoria, 3004, Australia
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Nedlands, Western Australia, 6009, Australia
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Graz, A-8036, Austria
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Innsbruck, 6020, Austria
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Salzburg, A-5020, Austria
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Vienna, 1090, Austria
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Vienna, A-1030, Austria
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Brasschaat, 2930, Belgium
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Brussels, 1090, Belgium
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Brussels, 1200, Belgium
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Ghent, 9000, Belgium
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Kortrijk, 8500, Belgium
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Leuven, 3000, Belgium
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Namur, 5000, Belgium
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Wilrijk, 2610, Belgium
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Ijuí, Rio Grande do Sul, 98700-000, Brazil
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Itajaí, Santa Catarina, 88301-215, Brazil
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Sao Paulo - SP, 01323-900, Brazil
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Calgary, Alberta, T2N 4N2, Canada
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Kelowna, British Columbia, V1Y 5L3, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Winnipeg, Manitoba, R3E 0V9, Canada
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Halifax, Nova Scotia, B3H 2Y9, Canada
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Kingston, Ontario, K7L 5P9, Canada
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Oshawa, Ontario, L1G 2B9, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Montreal, Quebec, H2L 4M1, Canada
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Québec, Quebec, G1R 2J6, Canada
Novartis Investigative Site
Olomouc, 775 20, Czechia
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Ostrava, 708 52, Czechia
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Prague, 100 34, Czechia
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Prague, 128 08, Czechia
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Zlín, 76275, Czechia
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Arhus C, 8000, Denmark
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Herlev, 2730, Denmark
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Odense, 5000 C, Denmark
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Helsinki, 00029, Finland
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Jyväskylä, 40620, Finland
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Tampere, 33520, Finland
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Turku, 20520, Finland
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Bordeaux, 33075, France
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Grenoble, 38043, France
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Lille, 59037, France
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Marseille, 13385, France
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Montpellier, 34295, France
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Nantes, 44093, France
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Nice, 06202, France
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Paris, 75475, France
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Reims, 51092, France
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Rennes, 35042, France
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Villejuif, 94805, France
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Heidelberg, Baden-Wurttemberg, 69120, Germany
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Heilbronn, Baden-Wurttemberg, 74078, Germany
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Mannheim, Baden-Wurttemberg, 68167, Germany
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Tübingen, Baden-Wurttemberg, 72076, Germany
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Erlangen, Bavaria, 91054, Germany
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Munich, Bavaria, 80337, Germany
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Munich, Bavaria, 80802, Germany
Novartis Investigative Site
Munich, Bavaria, 80804, Germany
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Nuremberg, Bavaria, 90419, Germany
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Regensburg, Bavaria, 93053, Germany
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Würzburg, Bavaria, 97080, Germany
Novartis Investigative Site
Buxtehude, Lower Saxony, 21614, Germany
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Hanover, Lower Saxony, 30625, Germany
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Bonn, North Rhine-Westphalia, 53127, Germany
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Cologne, North Rhine-Westphalia, 50937, Germany
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Essen, North Rhine-Westphalia, 45122, Germany
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Ludwigshafen am Rhein, Rhineland-Palatinate, 67063, Germany
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Mainz, Rhineland-Palatinate, 55131, Germany
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Dresden, Saxony, 01307, Germany
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Leipzig, Saxony, 04103, Germany
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Magdeburg, Saxony-Anhalt, 39120, Germany
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Kiel, Schleswig-Holstein, 24105, Germany
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Lübeck, Schleswig-Holstein, 23538, Germany
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Erfurt, Thuringia, 99089, Germany
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Gera, Thuringia, 07548, Germany
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Budapest, 1062, Hungary
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Budapest, H-1122, Hungary
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Debrecen, 4032, Hungary
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Győr, H-9024, Hungary
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Kaposvár, 7400, Hungary
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Miskolc, 3526, Hungary
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Szeged, 6720, Hungary
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Co.Cork, Ireland
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Dublin, 4, Ireland
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Dublin, 7, Ireland
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Dublin, 9, Ireland
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Galway, Ireland
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Jerusalem, Israel
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Ramat Gan, 52621, Israel
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Napoli, Campania, 80131, Italy
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Rome, Lazio, 00167, Italy
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Genoa, Liguria, 16132, Italy
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Bergamo, Lombardy, 24128, Italy
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Milan, Lombardy, 20133, Italy
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Milan, Lombardy, 20141, Italy
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Pisa, Tuscany, 56126, Italy
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Padua, Veneto, 35128, Italy
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Amsterdam, 1066 CX, Netherlands
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Amsterdam, 1081 HV, Netherlands
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Groningen, 9713 GZ, Netherlands
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Leeuwarden, 8934 AD, Netherlands
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Leiden, 2333 ZA, Netherlands
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Rotterdam, 3015 GD, Netherlands
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Christchurch, 8011, New Zealand
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Newtown, Wellington, 6002, New Zealand
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Kristiansand, 4604, Norway
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Lorenskog, 1478, Norway
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Oslo, 0310, Norway
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Gdansk, 80-215, Poland
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Konin, 62-500, Poland
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Poznan, 60-693, Poland
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Warsaw, 02-781, Poland
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Chelyabinsk, 454087, Russia
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Magnitogorsk, 455001, Russia
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Moscow, 115478, Russia
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Moscow, 143423, Russia
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Nizhny Novgorod, 603081, Russia
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Ryazan, 390011, Russia
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Saint Petersburg, 197758, Russia
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Goyang-si, Gyeonggi-Do, 410-769, South Korea
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Seoul, 03080, South Korea
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Seoul, 135-710, South Korea
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Barcelona, 08036, Spain
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Hospitalet de Llobregat, Barcelona, 08907, Spain
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Las Palmas de Gran Canaria, 35016, Spain
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Madrid, 28007, Spain
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Madrid, 28050, Spain
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Palma de Mallorca, 07010, Spain
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Pamplona, 31008, Spain
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Valencia, 46009, Spain
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Valencia, 46014, Spain
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Linköping, SE-581 85, Sweden
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Umeå, SE-901 85, Sweden
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Basel, 4031, Switzerland
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Lausanne, 1011, Switzerland
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Zurich, 8091, Switzerland
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Tainan, 704, Taiwan
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Taipei, 100, Taiwan
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Taoyuan District, 333, Taiwan
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Dnipropetrovsk, 49102, Ukraine
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Donetsk, 83092, Ukraine
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Kharkiv, 61070, Ukraine
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Kyiv, 03022, Ukraine
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Lviv, 79031, Ukraine
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Sumy, 40005, Ukraine
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Uzhhorod, 88017, Ukraine
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Cambridge, CB2 0QQ, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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London, NW3 2QG, United Kingdom
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London, SE1 7EH, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Southampton, SO16 6YD, United Kingdom
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Swansea, SA2 8QA, United Kingdom
Related Publications (5)
Schadendorf D, Robert C, Dummer R, Flaherty KT, Tawbi HA, Menzies AM, Banerjee H, Lau M, Long GV. Pyrexia in patients treated with dabrafenib plus trametinib across clinical trials in BRAF-mutant cancers. Eur J Cancer. 2021 Aug;153:234-241. doi: 10.1016/j.ejca.2021.05.005. Epub 2021 Jul 2.
PMID: 34225229DERIVEDRobert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E, Chiarion Sileni V, Schachter J, Garbe C, Bondarenko I, Gogas H, Mandala M, Haanen JBAG, Lebbe C, Mackiewicz A, Rutkowski P, Nathan PD, Ribas A, Davies MA, Flaherty KT, Burgess P, Tan M, Gasal E, Voi M, Schadendorf D, Long GV. Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma. N Engl J Med. 2019 Aug 15;381(7):626-636. doi: 10.1056/NEJMoa1904059. Epub 2019 Jun 4.
PMID: 31166680DERIVEDLong GV, Grob JJ, Nathan P, Ribas A, Robert C, Schadendorf D, Lane SR, Mak C, Legenne P, Flaherty KT, Davies MA. Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials. Lancet Oncol. 2016 Dec;17(12):1743-1754. doi: 10.1016/S1470-2045(16)30578-2. Epub 2016 Nov 16.
PMID: 27864013DERIVEDGrob JJ, Amonkar MM, Karaszewska B, Schachter J, Dummer R, Mackiewicz A, Stroyakovskiy D, Drucis K, Grange F, Chiarion-Sileni V, Rutkowski P, Lichinitser M, Levchenko E, Wolter P, Hauschild A, Long GV, Nathan P, Ribas A, Flaherty K, Sun P, Legos JJ, McDowell DO, Mookerjee B, Schadendorf D, Robert C. Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-label, randomised trial. Lancet Oncol. 2015 Oct;16(13):1389-98. doi: 10.1016/S1470-2045(15)00087-X.
PMID: 26433819DERIVEDRobert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, Chiarion-Sileni V, Drucis K, Krajsova I, Hauschild A, Lorigan P, Wolter P, Long GV, Flaherty K, Nathan P, Ribas A, Martin AM, Sun P, Crist W, Legos J, Rubin SD, Little SM, Schadendorf D. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015 Jan 1;372(1):30-9. doi: 10.1056/NEJMoa1412690. Epub 2014 Nov 16.
PMID: 25399551DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Disclosure Office
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 10, 2012
First Posted
May 14, 2012
Study Start
June 4, 2012
Primary Completion
April 17, 2014
Study Completion
April 25, 2019
Last Updated
February 24, 2021
Results First Posted
December 4, 2014
Record last verified: 2021-02
Data Sharing
- IPD Sharing
- Will share
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.