Clinical trial NCT01909453: Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
Official title: A 2-part Phase III Randomized, Open Label, Multicenter Study of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Melanoma
Keywords: Melanoma
Cutaneous melanoma
Skin disease
Skin cancer
Skin Neoplasms
Neoplasm Metastasis
BRAF mutant
BRAF V600E
BRAF V600K
Cancer
LGX818
MEK162
vemurafenib
combination
BRAF inhibitor
resistance
The combination of a selective BRAF- and a MEK1/2-inhibitor
Prior immunotherapy
MEK inhibitor
Phase III
Combo 300, Combo 450
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-07-26
Enrollment: 921
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is 2-part, randomized, open label, multi-center, parallel group, phase III study comparing the efficacy and safety of LGX818 plus MEK162 to vemurafenib and LGX818 monotherapy in patients with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation. A total of approximately 900 patients will be randomized.

Part 1:

Patients will be randomized in a 1:1:1 ratio to one of 3 treatment arms:

1. LGX818 450 mg QD plus MEK162 45 mg BID (denoted as Combo 450 arm)
2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm) or
3. vemurafenib 960 mg BID (denoted as vemurafenib arm)

Part 2:

Patients will be randomized in a 3:1 ratio to one of the 2 treatment arms:

1. LGX818 300 mg QD plus MEK162 45 mg BID (denoted as Combo 300 arm) or
2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm)


Eligibility criteria: Inclusion Criteria:

* Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma (AJCC Stage IIIB, IIIC, or IV)
* Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization
* Naïve untreated patients or patients who have progressed on or after prior first line immunotherapy for resectable locally advanced or metastatic melanoma; prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy, radiotherapy or chemotherapy), except the administration of BRAF or MEK inhibitors
* Evidence of at least one measurable lesion as detected by radiological or photographic methods
* ECOG performance status of 0 or 1
* Adequate bone marrow, organ function, cardiac and laboratory parameters
* Normal functioning of daily living activities

Exclusion Criteria:

* Any untreated central nervous system (CNS) lesion
* Uveal and mucosal melanoma
* History of leptomeningeal metastases
* History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease
* Any previous systemic chemotherapy treatment, extensive radiotherapy or investigational agent other than immunotherapy, or patients who have received more than one line of immunotherapy for locally advanced unresectable or metastatic melanoma; Ipilimumab (adjuvant) or other immunotherapy treatment must have ended at least 6 weeks prior to randomization
* History of Gilbert's syndrome
* Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor
* Impaired cardiovascular function or clinically significant cardiovascular diseases
* Uncontrolled arterial hypertension despite medical treatment
* HIV positive or active Hepatitis B, and/or active Hepatitis C
* Impairment of gastrointestinal function
* 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

Primary outcomes:
measure: Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group
timeFrame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)
measure: Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group
timeFrame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group
Secondary outcomes:
measure: Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group
timeFrame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)
measure: Part 1: Overall Survival (OS)
timeFrame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
measure: Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
timeFrame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
measure: Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03
timeFrame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
measure: Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
timeFrame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
measure: Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values
timeFrame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
measure: Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade
timeFrame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
measure: Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
timeFrame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
measure: Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
timeFrame: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group
measure: Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
timeFrame: Baseline up to 30 days after last dose of study drug (up to 36 months)
measure: Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0
timeFrame: Baseline up to 30 days after last dose of study drug (up to 36 months)
measure: Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
timeFrame: Baseline up to 30 days after last dose of study drug (up to 36 months)
measure: Part 2: Number of Participants With Newly Occurring Notable ECG Values
timeFrame: Baseline up to 30 days after last dose of study drug (up to 36 months)
measure: Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade
timeFrame: Baseline up to 30 days after last dose of study drug (up to 36 months)
measure: Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
timeFrame: Baseline up to 30 days after last dose of study drug (up to 36 months)
measure: Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03
timeFrame: Baseline up to 30 days after last dose of study drug (up to 36 months)
measure: Part 2: Overall Survival (OS)
timeFrame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
measure: Part 1 and Part 2: Objective Response Rate (ORR)
timeFrame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
measure: Part 1 and Part 2: Time to Objective Response (TTR)
timeFrame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
measure: Part 1 and Part 2: Disease Control Rate (DCR)
timeFrame: From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
measure: Part 1 and Part 2: Duration of Response (DOR)
timeFrame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
measure: Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale
timeFrame: Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
measure: Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
timeFrame: Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
measure: Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
timeFrame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
measure: Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
timeFrame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
measure: Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
timeFrame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
measure: Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
timeFrame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
measure: Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
timeFrame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
measure: Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
timeFrame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
measure: Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
timeFrame: Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)
measure: Part 1: Plasma Concentrations of LGX 818
timeFrame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
measure: Part 2: Plasma Concentrations of LGX 818
timeFrame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
measure: Part 1: Plasma Concentrations of MEK162
timeFrame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
measure: Part 2: Plasma Concentrations of MEK162
timeFrame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
measure: Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
timeFrame: Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Retinal Consultants of Alabama P.C.
state: Alabama
city: Birmingham
country: United States
facility: UAB Callahan Eye Hospital
state: Alabama
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Birmingham
country: United States
facility: UAB The Kirklin Clinic
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group - Fayetteville
state: Arkansas
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers (Williams) - USOR
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers (Williams) - USOR
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Parker
country: United States
facility: Specialty Eye Care
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Boynton Beach
country: United States
facility: University Cancer Institute
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Eye & Ear Infirmary- Opthalmology
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Sciences System - Investigational Drug Service
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Sciences System
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Medical Center
state: Illinois
city: Niles
country: United States
facility: Oncology Specialists, SC
state: Illinois
city: Goshen
country: United States
facility: Goshen Center For Cancer Care
state: Indiana
city: Grand Rapids
country: United States
facility: Lack's Cancer Center at Mercy Health Saint Mary's
state: Michigan
city: Grand Rapids
country: United States
facility: Mercy Health Hauenstein Neuroscience Center Neuro-Ophthalmology (Clinic)
state: Michigan
city: Grand Rapids
country: United States
facility: Retina Specialists of Michigan
state: Michigan
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic Oncology Hem
state: Mississippi
city: Jackson
country: United States
facility: Jackson Oncology Associates - St. Dominic Hospital
state: Mississippi
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Rochester
country: United States
facility: Investigational Drug Service, Department of Pharmacy (Investigational Product)
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center - PPDS
state: New York
city: Tulsa
country: United States
facility: Tulsa Cancer Institute PLLC
state: Oklahoma
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic & Pharmacy
state: South Dakota
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Cancer Institute
state: Tennessee
city: Dallas
country: United States
facility: Dr. Dennis B. Kay (Ophthalmologist)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Alexandria
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Arlington
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists (Leesburg) - USOR
state: Virginia
city: Falls Church
country: United States
facility: Northern Virginia Ophthalmology Associates
state: Virginia
city: Gainesville
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital & Clinics
state: Washington
city: Caba
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Fundación Investigar
state: Ciudad Autónoma DE Buenosaires
city: Buenos Aires
country: Argentina
facility: Instituto Médico Especializado Alexander Fleming
state: Ciudad Autónoma DE Buenosaires
city: Gateshead
country: Australia
facility: Lake Macquarie Private Hospital
state: New South Wales
city: Southport
country: Australia
facility: Tasman Oncology Research
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Prahran
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Salvador
country: Brazil
facility: AMO - Assistência Multidisciplinar em Oncologia
state: Bahia
city: Recife
country: Brazil
facility: Instituto de Medicina Integral Professor Fernando Figueira
state: Pernambuco
city: Ijuí
country: Brazil
facility: Associação Hospital de Caridade Ijuí
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
state: RIO Grande DO SUL
city: Barretos
country: Brazil
facility: Fundação PIO XII
state: SÃO Paulo
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Rio de Janeiro
country: Brazil
facility: INCA Instituto Nacional de Cancer
city: Sao Paulo
country: Brazil
facility: Hospital BP Mirante
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Toronto
country: Canada
facility: SunnyBrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier De L'Universite De Montreal Hospital Notre Dame
state: Quebec
city: Montreal
country: Canada
facility: CHUM Notrea Dame Hospital
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health center
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval - L' Hotel - Dieu de Quebec
city: Bogotá
country: Colombia
facility: Hospital Universitario San Ignacio
state: Distrito Capital DE Bogotá
city: Brno
country: Czechia
facility: Mou/Mmci - Ppds
state: Jihomoravský KRAJ
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
state: Moravskoslezský KRAJ
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
state: Praha, Hlavní Mesto
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 2
country: Czechia
facility: General Faculty Hospital
city: Grenoble
country: France
facility: CHU de Grenoble
state: Isère
city: Lille
country: France
facility: CHRU de Lille - Hôpital Huriet
state: Nord
city: Lyon
country: France
facility: Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
state: Rhone
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
state: Sarthe
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Val-de-marne
city: Bordeaux
country: France
facility: Hopital Saint Andre Unite de Cancerologie Service de Dermatologie
city: Boulogne-Billancourt
country: France
facility: Centre Hospitalier Universitaire Ambroise Paré
city: Nice
country: France
facility: Groupe Hospitalier Archet I Et II
city: Paris
country: France
facility: Hopital Lariboisiere
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Paris
country: France
facility: Ophtalmologist office
city: Paris
country: France
facility: Hôpital Saint louis
city: Pierre Benite
country: France
facility: Hospices Civils de Lyon - Hopital Lyon Sud
city: Reims
country: France
facility: CHU de Reims - Hôpital Robert Debré
city: Strasbourg
country: France
facility: Nouvel Hopital Civil
city: Freiburg im Breisgau
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden-württemberg
city: Heidelberg
country: Germany
facility: University Clinic Heidelberg - PPDS
state: Baden-württemberg
city: Mannheim
country: Germany
facility: Klinikum Mannheim Universitätsklinikum gGmbH
state: Baden-württemberg
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-württemberg
city: Nuernberg
country: Germany
facility: Hautklinik, Klinikum Nürnberg, Universitätsklinik der Paracelsus Medizinischen Privatuniversität
state: Bavaria
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth GmbH
state: Bayern
city: München
country: Germany
facility: LMU Klinikum
state: Bayern
city: Regensburg
country: Germany
facility: Institut für Röntgendiagnostik
state: Bayern
city: Regensburg
country: Germany
facility: University Clinic Regensburg - PPDS
state: Bayern
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
state: Bayern
city: Kassel
country: Germany
facility: Klinikum Kassel
state: Hessen
city: Buxtehude
country: Germany
facility: Augenarztzentrum Buxtehude
state: Niedersachsen
city: Buxtehude
country: Germany
facility: Elben Klinken Stade ? Buxtehude
state: Niedersachsen
city: Bonn
country: Germany
facility: Augenklinik Universitätsklinikum Bonn
state: Nordrhein-westfalen
city: Minden
country: Germany
facility: Institut für Diagnostische Radiologie, Neuroradiologie und Nuklearmedizin
state: Nordrhein-westfalen
city: Minden
country: Germany
facility: Mühlenkreiskliniken - Johannes Wesling Klinikum Minden
state: Nordrhein-westfalen
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
state: Rheinland-pfalz
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg A.ö.R.
state: Sachsen-anhalt
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig AoR
state: Sachsen
city: Lübeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein, Campus Lubeck
state: Schleswig-holstein
city: Berlin
country: Germany
facility: Charite-Universitaetsmedizin Berlin
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Dresden
country: Germany
facility: University Hospital Carl Gustav Carus at the Technical University of Dresden
city: Dresden
country: Germany
facility: Überörtliche Radiologische Gemeinschaftspraxis Dresden
city: Erfurt
country: Germany
facility: Klinik fur Hautkrankheiten und Allergologie, Helios Hauttumorzentrum Erfurt, Helios Klinikum Erfurt
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt/Main
country: Germany
facility: Goethe-University Frankfurt/Main
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Radiologie
city: Gera
country: Germany
facility: Institut für Diagnostische und Interventionelle Radiologie
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH
city: Gera
country: Germany
facility: Klinik für Augenheilkunde
city: Hamburg
country: Germany
facility: Universitätsklinik Hamburg Eppendorf
city: Hannover
country: Germany
facility: Augenärzte am Kröpcke
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (Hannover Medical School)
city: Hannover
country: Germany
facility: Institut für Diagnostische und Interventionelle Radilogie
city: Heidelberg
country: Germany
facility: University Clinic Heidelberg - PPDS
city: Homburg
country: Germany
facility: Universität des Saarlandes
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein, Campus Kiel
city: Mannheim
country: Germany
facility: Augenklinik Universitätsklinikum Mannheim
city: Minden
country: Germany
facility: Augen-Praxis_Minden
city: Münster
country: Germany
facility: Fachklinik Hornheide Abteilung für Internistische Onkologie und Hämatologie
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg - Campus Nord
city: Regensburg
country: Germany
facility: Klinik & Poliklinik für Augenheilkunde
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: Internistische Schwerpunktpraxis Kardiologie Hämatologie Onkologie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
city: Neo Faliro
country: Greece
facility: Metropolitan Hospital
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
state: Hajdú-bihar
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
city: Ramat Gan
country: Israel
facility: Sheba Medical Center - PPDS
state: Tel-aviv
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - PPDS
city: Torrette Site
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
state: Ancona
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
state: Campania
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna Policlinico S Orsola Malpighi
state: Emilia-romagna
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico Di Roma
state: Lazio
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
state: Lazio
city: Roma
country: Italy
facility: Istituto Dermopatico dell'Immacolata IRCCS
state: Lazio
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico Di Roma
state: Lazio
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN
state: Lombardia
city: Lecco
country: Italy
facility: Azienda Ospedaliera Ospedale Di Lecco
state: Lombardia
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
state: Lombardia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda
state: Lombardia
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
state: Lombardia
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia (IRCCS)
state: Torino
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Terni
country: Italy
facility: Azienda Ospedaliera S Maria Di Terni
state: Umbria
city: Padua
country: Italy
facility: Clinica Oculistica
state: Veneto
city: Bari
country: Italy
facility: IRCCS Giovanni Paolo II Cancer Institute
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII
city: Genoa
country: Italy
facility: IRCCS Az. Osp. Universitaria San Martino- IST
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - I.R.C.C.S.
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo di Pavia
city: Ragusa
country: Italy
facility: Azienda Ospedaliera Civile Maria Paternò Arezzo Ragusa
city: Ragusa
country: Italy
facility: S. C. Oncologia Medica Presidio Ospedaliero Maria Paterno Arezzo
city: Rome
country: Italy
facility: Policlinico Universitario Campus Biomedico
city: Siena
country: Italy
facility: Azienza Ospedaliera Universitaria Senese
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia
city: Fukuoka-shi
country: Japan
facility: Kyushu University Hospital
state: Fukuoka
city: Matsumoto
country: Japan
facility: Shinshu University Hospital
state: Nagano
city: Niigata-shi
country: Japan
facility: Niigata Cancer Center Hospital
state: Niigata
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Osaka
country: Japan
facility: National Hospital Organization Osaka National Hospital
state: Ôsaka
city: Gangnam-gu
country: Korea, Republic of
facility: Samsung Medical Center - PPDS
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System - PPDS
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerologia
state: DF
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo LEON
city: Cancun
country: Mexico
facility: Cancun Oncology Center Galenia
state: Quintana ROO
city: Mexico
country: Mexico
facility: Medica Sur, S. A. B de C. V. (Centro de Investigación Farmacológica y Biotecnológica CIF-BIOTEC)
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: Friesland
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
state: Gelderland
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
state: Noord Holland
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
state: Noord-brabant
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum
state: Noord-brabant
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: Overijssel
city: Zwolle
country: Netherlands
facility: Isala Zwolle
state: Overijssel
city: Ariënsplein Enschede
country: Netherlands
facility: Medisch Spectrum Twente - Hospital
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum - Heerlen
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Rotterdam
country: Netherlands
facility: Erasmus MC-Daniel den Hoed Oncologisch Centrum
city: Oslo
country: Norway
facility: Oslo universitetssykehus HF, Utprøvingsenheten
city: Oslo
country: Norway
facility: Oslo universitetssykehus HF
city: Oslo
country: Norway
facility: Oslo Myeloma Center - PPDS
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Medyczne MAVIT Sp. z o.o.
state: Mazowieckie
city: Warszawa
country: Poland
facility: Lux Med
city: Lisbon
country: Portugal
facility: Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
state: Lisboa
city: Almada
country: Portugal
facility: Hospital Garcia de Orta*E.P.E.
state: Setúbal
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte, E.P.E- Hospital de Santa Maria
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n a N N Blokhin
city: Ryazan
country: Russian Federation
facility: Ryazan Clinical Hospital n.a. Semashko
city: Ryazan
country: Russian Federation
facility: Ryazan Regional Clinical Oncology Dispensary
city: St. Petersburg
country: Russian Federation
facility: Scientific Research Institute of Oncology n.a. N.N. Petrov
city: Singapore
country: Singapore
facility: National Cancer Centre - 30 Hospital Blvd
city: Singapore
country: Singapore
facility: Singapore General Hospital (SGH)
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Singapore
country: Singapore
facility: Singapore National Eye Research Centre
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav - PPDS
city: Poprad
country: Slovakia
facility: POKO POPRAD, s.r.o.
city: Pretoria
country: South Africa
facility: Steve Biko Academic Hospital
city: Pretoria
country: South Africa
facility: Mary Potter Oncology Centre
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez
state: Andalucía
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Cetir, Centre Mèdic, S.L
state: Cataluña
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
state: Murcia
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Seville
country: Spain
facility: Hospital Nuestra Señora de Valme
state: Sevilla
city: Alicante
country: Spain
facility: Hospital General Universitario Dr. Balmis
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Donostia-san Sebastián
country: Spain
facility: Onkologikoa
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: La Coruna
country: Spain
facility: Hospital Universitario A Coruña
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Malaga
country: Spain
facility: Hospital Civil (Hospital Regional Universitario de Malaga)
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Universitario Nuestra Sra de La Candelaria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia
city: Gavle
country: Sweden
facility: Gävle Sjukhus
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Linköping
country: Sweden
facility: Universitetssjukhuset i Linköping
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus Lund
city: Solna
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Uppsala
country: Sweden
facility: Uppsala Universitet
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Zurich Flughafen
country: Switzerland
facility: Universitätsspital Zürich
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty Gazi Hospital
city: Bornova
country: Turkey
facility: Ege University Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical aculty
city: Izmir
country: Turkey
facility: Sifa Universitesi Bornova Egitim Arastirma Hastanesi
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
state: Cambridgeshire
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Chelsea
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital
state: London, CITY OF
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
state: Wirral
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: York
city: Broomfield
country: United Kingdom
facility: Broomfield Hospital
city: Leeds
country: United Kingdom
facility: St James University Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust - PPDS
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital - NWCRN- PPDS
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Dummer R, Flaherty KT, Robert C, Arance A, de Groot JWB, Garbe C, Gogas HJ, Gutzmer R, Krajsova I, Liszkay G, Loquai C, Mandala M, Schadendorf D, Yamazaki N, di Pietro A, Cantey-Kiser J, Edwards M, Ascierto PA. COLUMBUS 5-Year Update: A Randomized, Open-Label, Phase III Trial of Encorafenib Plus Binimetinib Versus Vemurafenib or Encorafenib in Patients With BRAF V600-Mutant Melanoma. J Clin Oncol. 2022 Dec 20;40(36):4178-4188. doi: 10.1200/JCO.21.02659. Epub 2022 Jul 21.
citation: Gogas H, Dummer R, Ascierto PA, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Sileni VC, Dutriaux C, Yamazaki N, Loquai C, Queirolo P, Jan de Willem G, Sellier AT, Suissa J, Murris J, Gollerkeri A, Robert C, Flaherty KT. Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS). Eur J Cancer. 2021 Jul;152:116-128. doi: 10.1016/j.ejca.2021.04.028. Epub 2021 Jun 4.
citation: Gogas HJ, Flaherty KT, Dummer R, Ascierto PA, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Sileni VC, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Gollerkeri A, Pickard MD, Robert C. Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management. Eur J Cancer. 2019 Sep;119:97-106. doi: 10.1016/j.ejca.2019.07.016. Epub 2019 Aug 19.
citation: Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Chiarion Sileni V, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Moutouh-de Parseval LA, Pickard MD, Sandor V, Robert C, Flaherty KT. Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1315-1327. doi: 10.1016/S1470-2045(18)30497-2. Epub 2018 Sep 12.
citation: Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Chiarion-Sileni V, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Moutouh-de Parseval LA, Pickard MD, Sandor V, Robert C, Flaherty KT. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):603-615. doi: 10.1016/S1470-2045(18)30142-6. Epub 2018 Mar 21.