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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
Titles & IDs
Public title
Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
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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
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Secondary ID [1]
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C4221004
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Secondary ID [2]
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CMEK162B2301
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Universal Trial Number (UTN)
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Trial acronym
COLUMBUS
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group
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Assessment method [1]
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PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC/central review and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 square millimeter (mm\^2).
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Timepoint [1]
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From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)
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Primary outcome [2]
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Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group
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Assessment method [2]
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PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm\^2.
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Timepoint [2]
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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
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Secondary outcome [1]
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Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group
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Assessment method [1]
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PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm\^2.
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Timepoint [1]
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From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)
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Secondary outcome [2]
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Part 1: Overall Survival (OS)
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Assessment method [2]
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Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a death had not been observed by the date of analysis cutoff, OS was censored at the date of last contact.
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Timepoint [2]
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From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)
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Secondary outcome [3]
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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
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Assessment method [3]
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AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported.
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Timepoint [3]
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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
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Secondary outcome [4]
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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
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Assessment method [4]
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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 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to \>=grade 3.
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Timepoint [4]
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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
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Secondary outcome [5]
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Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
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Assessment method [5]
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Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) (millimeter of mercury \[mmHg\]): less than or equal to (\<=) 90 mmHg with decrease from baseline of greater than or equal to (\>=) 20 mmHg/\>= 160 mmHg with increase from baseline of \>=20 mmHg. Low/high diastolic blood pressure (DBP) \[mmHg\]: \<= 50 mmHg with decrease from baseline of \>=15 mmHg/\>=100 mmHg with increase from baseline of \>=15 mmHg. Low/high Pulse rate: \<=50 beats per minute (bpm) with decrease from baseline of \>=15 bpm/\>= 120 bpm with increase from baseline of \>=15 bpm. Low/high Weight \[kilogram\]: \>=20 percent (%) decrease from baseline/\>= 10% increase from baseline. Low/high Body temperature degree Celsius (C): \<= 36 degree C/\>= 37.5 degree C.
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Timepoint [5]
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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
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Secondary outcome [6]
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Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values
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Assessment method [6]
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Newly occurring notable ECG values were reported for QT (millisecond \[ms\]), QTcF (millisecond), QTcB (millisecond) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New greater than (\>) 450, New \>480, New \>500, Increase from baseline \>30, Increase from baseline \>60. Heart rate: New \<60, New \>100 was considered as newly occurring notable value.
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Timepoint [6]
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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
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Secondary outcome [7]
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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
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Assessment method [7]
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Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline \>=10% and \< 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline \>=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations.
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Timepoint [7]
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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
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Secondary outcome [8]
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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
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Assessment method [8]
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AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and Palmar-plantar erythrodysaesthesia (PPE) syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
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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
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Secondary outcome [9]
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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
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Assessment method [9]
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AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding retinal vein occlusion (RVO), RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
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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
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Secondary outcome [10]
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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
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Assessment method [10]
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0
AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported.
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Timepoint [10]
0
0
Baseline up to 30 days after last dose of study drug (up to 36 months)
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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
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Assessment method [11]
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0
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 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to \>=grade 3.
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Timepoint [11]
0
0
Baseline up to 30 days after last dose of study drug (up to 36 months)
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Secondary outcome [12]
0
0
Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
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Assessment method [12]
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0
Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) in millimeter of mercury (mmHg): less than or equal to (\<=) 90 mmHg with decrease from baseline of greater than or equal to (\>=) 20 mmHg/\>= 160 mmHg with increase from baseline of \>=20 mmHg, Low/high diastolic blood pressure (DBP) \[mmHg\]: \<=50 mmHg with decrease from baseline of \>=15 mmHg/\>=100 mmHg with increase from baseline of \>=15 mmHg, Low/high pulse rate \[bpm\]: \<=50 bpm with decrease from baseline of \>=15 bpm/\>=120 bpm with increase from baseline of \>=15 bpm, Low/high weight (kg): \>=20 % decrease from baseline/\>= 10% increase from baseline Low/high Body temperature degree C): \<= 36°C/\>= 37.5 degree C.
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Timepoint [12]
0
0
Baseline up to 30 days after last dose of study drug (up to 36 months)
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Secondary outcome [13]
0
0
Part 2: Number of Participants With Newly Occurring Notable ECG Values
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Assessment method [13]
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0
Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (bpm). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New \>450, New \>480, New \>500, increase from baseline \>30, Increase from baseline \>60. Heart rate: New \< 60, New \>100 was considered as newly occurring notable value.
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Timepoint [13]
0
0
Baseline up to 30 days after last dose of study drug (up to 36 months)
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Secondary outcome [14]
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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
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Assessment method [14]
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0
Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline \>=10% and \< 20%;Grade 3: LVEF between 20% and 39% or absolute reduction from baseline \>=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations.
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Timepoint [14]
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0
Baseline up to 30 days after last dose of study drug (up to 36 months)
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Secondary outcome [15]
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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
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Assessment method [15]
0
0
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and PPE syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported are reported in this outcome measure.
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Timepoint [15]
0
0
Baseline up to 30 days after last dose of study drug (up to 36 months)
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Secondary outcome [16]
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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
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Assessment method [16]
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0
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding RVO, RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure.
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Timepoint [16]
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0
Baseline up to 30 days after last dose of study drug (up to 36 months)
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Secondary outcome [17]
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0
Part 2: Overall Survival (OS)
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Assessment method [17]
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0
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Timepoint [17]
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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)
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Secondary outcome [18]
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0
Part 1 and Part 2: Objective Response Rate (ORR)
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Assessment method [18]
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ORR, calculated as the percentage of participants with a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Results are reported for confirmed BIRC response.
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Timepoint [18]
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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)
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Secondary outcome [19]
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Part 1 and Part 2: Time to Objective Response (TTR)
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Assessment method [19]
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TTR was the time between date of randomization until first documented response of CR or PR. Participants who did not achieve a PR or CR were censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. first patient first visit \[FPFV\] to last patient last visit \[LPLV\] used for the analysis) when they had a PFS event. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. TTR was estimated in the treatment arms using a Kaplan-Meier method. TTR was based on central review.
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Timepoint [19]
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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)
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Secondary outcome [20]
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Part 1 and Part 2: Disease Control Rate (DCR)
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Assessment method [20]
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DCR was calculated as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Two sets of DCR were considered, one for confirmed and one for unconfirmed responses. Results are reported for confirmed and unconfirmed responses combined. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. DCR was based on central review.
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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)
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Secondary outcome [21]
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0
Part 1 and Part 2: Duration of Response (DOR)
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Assessment method [21]
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DOR was calculated, as the time from the date of first documented response (CR or PR) to the first documented progression or death due to underlying cancer. DOR was estimated for responders (i.e. participants achieving at least once CR or PR) only using a Kaplan-Meier method. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a participant with a CR or PR had no progression or death due to underlying disease, the participant was censored at the date of last adequate tumor assessment. Results are based on confirmed BIRC response.
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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)
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Secondary outcome [22]
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0
Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale
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Assessment method [22]
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0
FACT-M:melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs,symptoms,physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items,not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores.Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represent better quality of life.Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. Time to definitive 10% deterioration:time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause.
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Timepoint [22]
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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)
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Secondary outcome [23]
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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)
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Assessment method [23]
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0
EORTC QLQ-C30 is 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4 point Likert scales with responses from "not at all" to "very much" and two 7 point Likert scales for global health and overall QOL. Global health status scale score ranged from 0 to 100. Higher score represented better level of functioning. Time to definitive 10% deterioration: time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause.
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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)
Query!
Secondary outcome [24]
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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
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Assessment method [24]
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0
FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life.
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Timepoint [24]
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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)
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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
Query!
Assessment method [25]
0
0
EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Query!
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)
Query!
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
Query!
Assessment method [26]
0
0
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms.
Query!
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)
Query!
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
Query!
Assessment method [27]
0
0
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Query!
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)
Query!
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
Query!
Assessment method [28]
0
0
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Query!
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)
Query!
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
Query!
Assessment method [29]
0
0
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Query!
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)
Query!
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)
Query!
Assessment method [30]
0
0
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead.
Query!
Timepoint [30]
0
0
Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)
Query!
Secondary outcome [31]
0
0
Part 1: Plasma Concentrations of LGX 818
Query!
Assessment method [31]
0
0
Query!
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
Query!
Secondary outcome [32]
0
0
Part 2: Plasma Concentrations of LGX 818
Query!
Assessment method [32]
0
0
Query!
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
Query!
Secondary outcome [33]
0
0
Part 1: Plasma Concentrations of MEK162
Query!
Assessment method [33]
0
0
Query!
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
Query!
Secondary outcome [34]
0
0
Part 2: Plasma Concentrations of MEK162
Query!
Assessment method [34]
0
0
Query!
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
Query!
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)
Query!
Assessment method [35]
0
0
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair \>50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Definitive deterioration was defined as death due to any cause or decrease in ECOG PS by at least one category from baseline score with no subsequent improvement.
Query!
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)
Query!
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
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Active, not recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
16/09/2013
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
31/08/2024
Query!
Actual
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
921
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Query!
Recruitment hospital [1]
0
0
Lake Macquarie Private Hospital - Gateshead
Query!
Recruitment hospital [2]
0
0
HPS Pharmacy - Southport
Query!
Recruitment hospital [3]
0
0
Tasman Oncology Research - Southport
Query!
Recruitment hospital [4]
0
0
Vision Optical - Southport
Query!
Recruitment hospital [5]
0
0
Princess Alexandra Hospital - Woolloongabba
Query!
Recruitment hospital [6]
0
0
The Alfred Hospital - Melbourne
Query!
Recruitment hospital [7]
0
0
The Alfred Hospital - Prahran
Query!
Recruitment hospital [8]
0
0
Sir Charles Gairdner Hospital Pharmacy Department - Nedlands
Query!
Recruitment hospital [9]
0
0
Sir Charles Gairdner Hospital - Nedlands
Query!
Recruitment postcode(s) [1]
0
0
02290 - Gateshead
Query!
Recruitment postcode(s) [2]
0
0
4215 - Southport
Query!
Recruitment postcode(s) [3]
0
0
4102 - Woolloongabba
Query!
Recruitment postcode(s) [4]
0
0
3004 - Melbourne
Query!
Recruitment postcode(s) [5]
0
0
3004 - Prahran
Query!
Recruitment postcode(s) [6]
0
0
6009 - Nedlands
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Alabama
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Arkansas
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
California
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Colorado
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Illinois
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Indiana
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Michigan
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Mississippi
Query!
Country [9]
0
0
United States of America
Query!
State/province [9]
0
0
New Jersey
Query!
Country [10]
0
0
United States of America
Query!
State/province [10]
0
0
New York
Query!
Country [11]
0
0
United States of America
Query!
State/province [11]
0
0
Texas
Query!
Country [12]
0
0
United States of America
Query!
State/province [12]
0
0
Vermont
Query!
Country [13]
0
0
United States of America
Query!
State/province [13]
0
0
Virginia
Query!
Country [14]
0
0
United States of America
Query!
State/province [14]
0
0
Washington
Query!
Country [15]
0
0
Argentina
Query!
State/province [15]
0
0
Buenos Aires
Query!
Country [16]
0
0
Argentina
Query!
State/province [16]
0
0
Ciudad Autónoma DE Buenosaires
Query!
Country [17]
0
0
Brazil
Query!
State/province [17]
0
0
Pernambuco
Query!
Country [18]
0
0
Brazil
Query!
State/province [18]
0
0
RIO Grande DO SUL
Query!
Country [19]
0
0
Brazil
Query!
State/province [19]
0
0
SÃO Paulo
Query!
Country [20]
0
0
Brazil
Query!
State/province [20]
0
0
Natal
Query!
Country [21]
0
0
Brazil
Query!
State/province [21]
0
0
Rio de Janeiro
Query!
Country [22]
0
0
Brazil
Query!
State/province [22]
0
0
Sao Paulo
Query!
Country [23]
0
0
Canada
Query!
State/province [23]
0
0
Alberta
Query!
Country [24]
0
0
Canada
Query!
State/province [24]
0
0
Ontario
Query!
Country [25]
0
0
Canada
Query!
State/province [25]
0
0
Quebec
Query!
Country [26]
0
0
Colombia
Query!
State/province [26]
0
0
Distrito Capital DE Bogotá
Query!
Country [27]
0
0
Colombia
Query!
State/province [27]
0
0
Pbx (57-1)
Query!
Country [28]
0
0
Czechia
Query!
State/province [28]
0
0
Jihomoravský KRAJ
Query!
Country [29]
0
0
Czechia
Query!
State/province [29]
0
0
Moravskoslezský KRAJ
Query!
Country [30]
0
0
Czechia
Query!
State/province [30]
0
0
Praha, Hlavní Mesto
Query!
Country [31]
0
0
Czechia
Query!
State/province [31]
0
0
Brno
Query!
Country [32]
0
0
Czechia
Query!
State/province [32]
0
0
Olomouc
Query!
Country [33]
0
0
Czechia
Query!
State/province [33]
0
0
Ostrava Poruba
Query!
Country [34]
0
0
Czechia
Query!
State/province [34]
0
0
Praha 2
Query!
Country [35]
0
0
Czechia
Query!
State/province [35]
0
0
Praha
Query!
Country [36]
0
0
France
Query!
State/province [36]
0
0
Alpes-maritimes
Query!
Country [37]
0
0
France
Query!
State/province [37]
0
0
Gironde
Query!
Country [38]
0
0
France
Query!
State/province [38]
0
0
Isère
Query!
Country [39]
0
0
France
Query!
State/province [39]
0
0
Marne
Query!
Country [40]
0
0
France
Query!
State/province [40]
0
0
Nord
Query!
Country [41]
0
0
France
Query!
State/province [41]
0
0
Rhone
Query!
Country [42]
0
0
France
Query!
State/province [42]
0
0
Rhône
Query!
Country [43]
0
0
France
Query!
State/province [43]
0
0
Sarthe
Query!
Country [44]
0
0
France
Query!
State/province [44]
0
0
Val-de-marne
Query!
Country [45]
0
0
France
Query!
State/province [45]
0
0
Bordeaux
Query!
Country [46]
0
0
France
Query!
State/province [46]
0
0
Boulogne-Billancourt
Query!
Country [47]
0
0
France
Query!
State/province [47]
0
0
Lille
Query!
Country [48]
0
0
France
Query!
State/province [48]
0
0
Lyon
Query!
Country [49]
0
0
France
Query!
State/province [49]
0
0
Nice
Query!
Country [50]
0
0
France
Query!
State/province [50]
0
0
Paris
Query!
Country [51]
0
0
France
Query!
State/province [51]
0
0
Pierre Benite
Query!
Country [52]
0
0
France
Query!
State/province [52]
0
0
Pierre-bénite
Query!
Country [53]
0
0
France
Query!
State/province [53]
0
0
Reims
Query!
Country [54]
0
0
France
Query!
State/province [54]
0
0
Strasbourg
Query!
Country [55]
0
0
France
Query!
State/province [55]
0
0
Templemars
Query!
Country [56]
0
0
France
Query!
State/province [56]
0
0
Villejuif
Query!
Country [57]
0
0
Germany
Query!
State/province [57]
0
0
Baden-württemberg
Query!
Country [58]
0
0
Germany
Query!
State/province [58]
0
0
Bavaria
Query!
Country [59]
0
0
Germany
Query!
State/province [59]
0
0
Bayern
Query!
Country [60]
0
0
Germany
Query!
State/province [60]
0
0
Hessen
Query!
Country [61]
0
0
Germany
Query!
State/province [61]
0
0
Niedersachsen
Query!
Country [62]
0
0
Germany
Query!
State/province [62]
0
0
Nordrhein-westfalen
Query!
Country [63]
0
0
Germany
Query!
State/province [63]
0
0
Rheinland-pfalz
Query!
Country [64]
0
0
Germany
Query!
State/province [64]
0
0
Sachsen-anhalt
Query!
Country [65]
0
0
Germany
Query!
State/province [65]
0
0
Sachsen
Query!
Country [66]
0
0
Germany
Query!
State/province [66]
0
0
Schleswig-holstein
Query!
Country [67]
0
0
Germany
Query!
State/province [67]
0
0
Berlin
Query!
Country [68]
0
0
Germany
Query!
State/province [68]
0
0
Bonn
Query!
Country [69]
0
0
Germany
Query!
State/province [69]
0
0
Dresden
Query!
Country [70]
0
0
Germany
Query!
State/province [70]
0
0
Erfurt
Query!
Country [71]
0
0
Germany
Query!
State/province [71]
0
0
Essen
Query!
Country [72]
0
0
Germany
Query!
State/province [72]
0
0
Frankfurt/Main
Query!
Country [73]
0
0
Germany
Query!
State/province [73]
0
0
Freiburg
Query!
Country [74]
0
0
Germany
Query!
State/province [74]
0
0
Gera
Query!
Country [75]
0
0
Germany
Query!
State/province [75]
0
0
Hamburg
Query!
Country [76]
0
0
Germany
Query!
State/province [76]
0
0
Hannover
Query!
Country [77]
0
0
Germany
Query!
State/province [77]
0
0
Heidelberg
Query!
Country [78]
0
0
Germany
Query!
State/province [78]
0
0
Homburg
Query!
Country [79]
0
0
Germany
Query!
State/province [79]
0
0
Kiel
Query!
Country [80]
0
0
Germany
Query!
State/province [80]
0
0
Lübeck
Query!
Country [81]
0
0
Germany
Query!
State/province [81]
0
0
Magdeburg
Query!
Country [82]
0
0
Germany
Query!
State/province [82]
0
0
Mainz
Query!
Country [83]
0
0
Germany
Query!
State/province [83]
0
0
Mannheim
Query!
Country [84]
0
0
Germany
Query!
State/province [84]
0
0
Minden
Query!
Country [85]
0
0
Germany
Query!
State/province [85]
0
0
München
Query!
Country [86]
0
0
Germany
Query!
State/province [86]
0
0
Münster
Query!
Country [87]
0
0
Germany
Query!
State/province [87]
0
0
Nürnberg
Query!
Country [88]
0
0
Germany
Query!
State/province [88]
0
0
Regensburg
Query!
Country [89]
0
0
Germany
Query!
State/province [89]
0
0
Tübingen
Query!
Country [90]
0
0
Germany
Query!
State/province [90]
0
0
Ulm
Query!
Country [91]
0
0
Greece
Query!
State/province [91]
0
0
Attiki
Query!
Country [92]
0
0
Greece
Query!
State/province [92]
0
0
Athens
Query!
Country [93]
0
0
Greece
Query!
State/province [93]
0
0
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Funding & Sponsors
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Commercial sector/industry
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Pfizer
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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)
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Trial website
https://clinicaltrials.gov/study/NCT01909453
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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.
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Public notes
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Contacts
Principal investigator
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Pfizer CT.gov Call Center
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Pfizer
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01909453