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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01909453




Registration number
NCT01909453
Ethics application status
Date submitted
24/07/2013
Date registered
26/07/2013
Date last updated
5/11/2024

Titles & IDs
Public title
Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
Scientific 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
Secondary ID [1] 0 0
C4221004
Secondary ID [2] 0 0
CMEK162B2301
Universal Trial Number (UTN)
Trial acronym
COLUMBUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LGX818
Treatment: Drugs - MEK162
Treatment: Drugs - vemurafenib

Experimental: LGX818 450 mg + MEK162 - LGX818 450 mg QD + MEK162 45 mg BID

Active comparator: Vemurafenib - Vemurafenib 960 mg BID

Experimental: LGX818 300 mg + MEK162 - LGX818 300 mg QD + MEK162 45 mg BID

Experimental: LGX818 - LGX818 300 mg QD


Treatment: Drugs: LGX818
LGX818- Orally 100 mg and 50 mg capsules

Treatment: Drugs: MEK162
MEK162- Orally 15 mg tablets

Treatment: Drugs: vemurafenib
Tablets in bottles or blisters 240 mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group
Timepoint [1] 0 0
From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)
Primary outcome [2] 0 0
Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group
Timepoint [2] 0 0
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 outcome [1] 0 0
Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group
Timepoint [1] 0 0
From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)
Secondary outcome [2] 0 0
Part 1: Overall Survival (OS)
Timepoint [2] 0 0
From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
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
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Baseline up to 30 days after last dose of study drug (up to 36 months)
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
Baseline up to 30 days after last dose of study drug (up to 36 months)
Secondary outcome [12] 0 0
Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Timepoint [12] 0 0
Baseline up to 30 days after last dose of study drug (up to 36 months)
Secondary outcome [13] 0 0
Part 2: Number of Participants With Newly Occurring Notable ECG Values
Timepoint [13] 0 0
Baseline up to 30 days after last dose of study drug (up to 36 months)
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
Baseline up to 30 days after last dose of study drug (up to 36 months)
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
Baseline up to 30 days after last dose of study drug (up to 36 months)
Secondary outcome [16] 0 0
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
Timepoint [16] 0 0
Baseline up to 30 days after last dose of study drug (up to 36 months)
Secondary outcome [17] 0 0
Part 2: Overall Survival (OS)
Timepoint [17] 0 0
From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
Secondary outcome [18] 0 0
Part 1 and Part 2: Objective Response Rate (ORR)
Timepoint [18] 0 0
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)
Secondary outcome [19] 0 0
Part 1 and Part 2: Time to Objective Response (TTR)
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
Part 1 and Part 2: Disease Control Rate (DCR)
Timepoint [20] 0 0
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)
Secondary outcome [21] 0 0
Part 1 and Part 2: Duration of Response (DOR)
Timepoint [21] 0 0
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)
Secondary outcome [22] 0 0
Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale
Timepoint [22] 0 0
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)
Secondary outcome [23] 0 0
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)
Timepoint [23] 0 0
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)
Secondary outcome [24] 0 0
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
Timepoint [24] 0 0
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)
Secondary outcome [25] 0 0
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
Timepoint [25] 0 0
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)
Secondary outcome [26] 0 0
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
Timepoint [26] 0 0
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)
Secondary outcome [27] 0 0
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
Timepoint [27] 0 0
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)
Secondary outcome [28] 0 0
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
Timepoint [28] 0 0
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)
Secondary outcome [29] 0 0
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
Timepoint [29] 0 0
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)
Secondary outcome [30] 0 0
Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Timepoint [30] 0 0
Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)
Secondary outcome [31] 0 0
Part 1: Plasma Concentrations of LGX 818
Timepoint [31] 0 0
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
Secondary outcome [32] 0 0
Part 2: Plasma Concentrations of LGX 818
Timepoint [32] 0 0
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
Secondary outcome [33] 0 0
Part 1: Plasma Concentrations of MEK162
Timepoint [33] 0 0
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
Secondary outcome [34] 0 0
Part 2: Plasma Concentrations of MEK162
Timepoint [34] 0 0
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
Secondary outcome [35] 0 0
Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Timepoint [35] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/09/2024
Sample size
Target
Accrual to date
Final
921
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Lake Macquarie Private Hospital - Gateshead
Recruitment hospital [2] 0 0
HPS Pharmacy - Southport
Recruitment hospital [3] 0 0
Tasman Oncology Research - Southport
Recruitment hospital [4] 0 0
Vision Optical - Southport
Recruitment hospital [5] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [7] 0 0
The Alfred Hospital - Prahran
Recruitment hospital [8] 0 0
Sir Charles Gairdner Hospital Pharmacy Department - Nedlands
Recruitment hospital [9] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
02290 - Gateshead
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3004 - Prahran
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
Country [10] 0 0
United States of America
State/province [10] 0 0
New Jersey
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Vermont
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Argentina
State/province [16] 0 0
Buenos Aires
Country [17] 0 0
Argentina
State/province [17] 0 0
Ciudad Autónoma DE Buenosaires
Country [18] 0 0
Brazil
State/province [18] 0 0
Pernambuco
Country [19] 0 0
Brazil
State/province [19] 0 0
RIO Grande DO SUL
Country [20] 0 0
Brazil
State/province [20] 0 0
SÃO Paulo
Country [21] 0 0
Brazil
State/province [21] 0 0
Natal
Country [22] 0 0
Brazil
State/province [22] 0 0
Rio de Janeiro
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Canada
State/province [24] 0 0
Alberta
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
Colombia
State/province [27] 0 0
Distrito Capital DE Bogotá
Country [28] 0 0
Colombia
State/province [28] 0 0
Pbx (57-1)
Country [29] 0 0
Czechia
State/province [29] 0 0
Jihomoravský KRAJ
Country [30] 0 0
Czechia
State/province [30] 0 0
Moravskoslezský KRAJ
Country [31] 0 0
Czechia
State/province [31] 0 0
Praha, Hlavní Mesto
Country [32] 0 0
Czechia
State/province [32] 0 0
Brno
Country [33] 0 0
Czechia
State/province [33] 0 0
Olomouc
Country [34] 0 0
Czechia
State/province [34] 0 0
Ostrava Poruba
Country [35] 0 0
Czechia
State/province [35] 0 0
Praha 2
Country [36] 0 0
Czechia
State/province [36] 0 0
Praha
Country [37] 0 0
France
State/province [37] 0 0
Alpes-maritimes
Country [38] 0 0
France
State/province [38] 0 0
Gironde
Country [39] 0 0
France
State/province [39] 0 0
Isère
Country [40] 0 0
France
State/province [40] 0 0
Marne
Country [41] 0 0
France
State/province [41] 0 0
Nord
Country [42] 0 0
France
State/province [42] 0 0
Rhone
Country [43] 0 0
France
State/province [43] 0 0
Rhône
Country [44] 0 0
France
State/province [44] 0 0
Sarthe
Country [45] 0 0
France
State/province [45] 0 0
Val-de-marne
Country [46] 0 0
France
State/province [46] 0 0
Bordeaux
Country [47] 0 0
France
State/province [47] 0 0
Boulogne-Billancourt
Country [48] 0 0
France
State/province [48] 0 0
Lille
Country [49] 0 0
France
State/province [49] 0 0
Lyon
Country [50] 0 0
France
State/province [50] 0 0
Nice
Country [51] 0 0
France
State/province [51] 0 0
Paris
Country [52] 0 0
France
State/province [52] 0 0
Pierre Benite
Country [53] 0 0
France
State/province [53] 0 0
Pierre-bénite
Country [54] 0 0
France
State/province [54] 0 0
Reims
Country [55] 0 0
France
State/province [55] 0 0
Strasbourg
Country [56] 0 0
France
State/province [56] 0 0
Templemars
Country [57] 0 0
France
State/province [57] 0 0
Villejuif
Country [58] 0 0
Germany
State/province [58] 0 0
Baden-württemberg
Country [59] 0 0
Germany
State/province [59] 0 0
Bavaria
Country [60] 0 0
Germany
State/province [60] 0 0
Bayern
Country [61] 0 0
Germany
State/province [61] 0 0
Hessen
Country [62] 0 0
Germany
State/province [62] 0 0
Niedersachsen
Country [63] 0 0
Germany
State/province [63] 0 0
Nordrhein-westfalen
Country [64] 0 0
Germany
State/province [64] 0 0
Rheinland-pfalz
Country [65] 0 0
Germany
State/province [65] 0 0
Sachsen-anhalt
Country [66] 0 0
Germany
State/province [66] 0 0
Sachsen
Country [67] 0 0
Germany
State/province [67] 0 0
Schleswig-holstein
Country [68] 0 0
Germany
State/province [68] 0 0
Berlin
Country [69] 0 0
Germany
State/province [69] 0 0
Bonn
Country [70] 0 0
Germany
State/province [70] 0 0
Dresden
Country [71] 0 0
Germany
State/province [71] 0 0
Erfurt
Country [72] 0 0
Germany
State/province [72] 0 0
Essen
Country [73] 0 0
Germany
State/province [73] 0 0
Frankfurt/Main
Country [74] 0 0
Germany
State/province [74] 0 0
Freiburg
Country [75] 0 0
Germany
State/province [75] 0 0
Gera
Country [76] 0 0
Germany
State/province [76] 0 0
Hamburg
Country [77] 0 0
Germany
State/province [77] 0 0
Hannover
Country [78] 0 0
Germany
State/province [78] 0 0
Heidelberg
Country [79] 0 0
Germany
State/province [79] 0 0
Homburg
Country [80] 0 0
Germany
State/province [80] 0 0
Kiel
Country [81] 0 0
Germany
State/province [81] 0 0
Lübeck
Country [82] 0 0
Germany
State/province [82] 0 0
Magdeburg
Country [83] 0 0
Germany
State/province [83] 0 0
Mainz
Country [84] 0 0
Germany
State/province [84] 0 0
Mannheim
Country [85] 0 0
Germany
State/province [85] 0 0
Minden
Country [86] 0 0
Germany
State/province [86] 0 0
München
Country [87] 0 0
Germany
State/province [87] 0 0
Münster
Country [88] 0 0
Germany
State/province [88] 0 0
Nürnberg
Country [89] 0 0
Germany
State/province [89] 0 0
Regensburg
Country [90] 0 0
Germany
State/province [90] 0 0
Tübingen
Country [91] 0 0
Germany
State/province [91] 0 0
Ulm
Country [92] 0 0
Greece
State/province [92] 0 0
Attiki
Country [93] 0 0
Greece
State/province [93] 0 0
Athens
Country [94] 0 0
Greece
State/province [94] 0 0
Neo Faliro
Country [95] 0 0
Greece
State/province [95] 0 0
Piraeus
Country [96] 0 0
Hungary
State/province [96] 0 0
Hajdú-bihar
Country [97] 0 0
Hungary
State/province [97] 0 0
Budapest
Country [98] 0 0
Hungary
State/province [98] 0 0
Debrecen
Country [99] 0 0
Hungary
State/province [99] 0 0
Szolnok
Country [100] 0 0
Israel
State/province [100] 0 0
Hatsafon
Country [101] 0 0
Israel
State/province [101] 0 0
Heifa
Country [102] 0 0
Israel
State/province [102] 0 0
Tel-aviv
Country [103] 0 0
Israel
State/province [103] 0 0
Haifa
Country [104] 0 0
Israel
State/province [104] 0 0
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Preston

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
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Ethics approval
Ethics application status

Summary
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)
Trial website
https://clinicaltrials.gov/study/NCT01909453
Trial related presentations / publications
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. Erratum In: J Clin Oncol. 2023 Apr 20;41(12):2301. doi: 10.1200/JCO.23.00385.
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. Erratum In: Eur J Cancer. 2022 Jan;160:287-288. doi: 10.1016/j.ejca.2021.10.002.
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.
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. Erratum In: Lancet Oncol. 2018 Oct;19(10):e509. doi: 10.1016/S1470-2045(18)30705-8.
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.
Public notes

Contacts
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Pfizer
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Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01909453