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A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma to the Brain (Break MB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01266967
Recruitment Status : Completed
First Posted : December 24, 2010
Results First Posted : March 5, 2014
Last Update Posted : May 8, 2014
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma and Brain Metastases
Intervention Drug: GSK2118436
Enrollment 172
Recruitment Details  
Pre-assignment Details  
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description Participants who received no prior local therapy for brain metastasis received GSK2118436 150 milligram (mg) capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events. Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Period Title: Overall Study
Started 89 83
Completed 0 0
Not Completed 89 83
Reason Not Completed
Death             69             61
Study Closed/Terminated             15             17
Lost to Follow-up             2             1
Physician Decision             0             1
Withdrawal by Subject             3             3
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy Total
Hide Arm/Group Description Participants who received no prior local therapy for brain metastasis received GSK2118436 150 milligram (mg) capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events. Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events. Total of all reporting groups
Overall Number of Baseline Participants 89 83 172
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 89 participants 83 participants 172 participants
52.3  (13.35) 52.7  (13.83) 52.5  (13.55)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 89 participants 83 participants 172 participants
Female
24
  27.0%
28
  33.7%
52
  30.2%
Male
65
  73.0%
55
  66.3%
120
  69.8%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 89 participants 83 participants 172 participants
White 89 82 171
Not reported 0 1 1
[1]
Measure Description: Race was not reported for one participant who recevied prior local therapy.
1.Primary Outcome
Title Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator
Hide Description OIR is defined as the number of participants whose intracranial response was a confirmed complete response (CR) or partial response (PR) assessed by investigators using modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters (e.g., percent change from Baseline). For the primary analysis, OIR was measured when all participants in both treatment arms had two post-Baseline disease assessments. Participants who had an intracranial response of not evaluable or a missing response were treated as non-responders. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment.
Time Frame From the time of the Baseline assessment until disease progression or end of study treatment (average of 18.3 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600E Population: all participants with BRAF V600E mutation-positive melanoma who received at least one dose of study treatment
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 74 65
Measure Type: Number
Unit of Measure: participants
CR 4 1
PR 26 23
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GSK2118436 150 mg: No Prior Local Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact Test
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 41
Confidence Interval (2-Sided) 95%
29.3 to 52.6
Estimation Comments The estimated value represents the percentage of participants with OIR.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection GSK2118436 150 mg: Prior Local Therapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact Test
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 37
Confidence Interval (2-Sided) 95%
25.3 to 49.8
Estimation Comments The estimated value represents the percentage of participants with OIR.
2.Secondary Outcome
Title Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator
Hide Description OR is defined as the number of participants achieving either a CR (the disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) per modified RECIST, version 1.1. To determine the OR, the extracranial response was combined with the intracranial response. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol-scheduled assessment. Participants who had an overall response of not evaluable or a missing response were treated as non-responders.
Time Frame From the time of the Baseline assessment until disease progression or end of study treatment (average of 24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600E Population
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 74 65
Measure Type: Number
Unit of Measure: participants
CR 2 0
PR 28 23
3.Secondary Outcome
Title Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator
Hide Description OR is defined as the number of participants achieving either a CR (the disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) per modified RECIST, version 1.1. To determine the OR, the extracranial response was combined with the intracranial response. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol-scheduled assessment. Participants who had an overall response of not evaluable or a missing response were treated as non-responders.
Time Frame From the time of the Baseline assessment until disease progression or end of study treatment (average of 17 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600K Population: all participants with BRAF V600K mutation-positive melanoma who received at least one dose of study treatment
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: participants
CR 0 0
PR 0 5
4.Secondary Outcome
Title Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator
Hide Description OIR is defined as the number of participants whose intracranial response was a confirmed complete response (CR) or partial response (PF) assessed by investigators using modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters (e.g., percent change from Baseline). For the primary analysis, OIR was measured when all participants in both treatment arms had two post-Baseline disease assessments. Participants who had an intracranial response of not evaluable or a missing response were treated as non-responders. Confirmation assessments were to be performed no less than 4 weeks after the criteria for response were initially met and may have been performed at the next protocol scheduled assessment.
Time Frame From the time of the Baseline assessment until disease progression or end of study treatment (average of 16 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600K Population
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 15 18
Measure Type: Number
Unit of Measure: participants
CR 0 0
PR 1 4
5.Secondary Outcome
Title Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants
Hide Description Duration of Intracranial Response is defined as the time from the first documented evidence of intracranial CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) until the time of the first documented intracranial disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).
Time Frame Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 27 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600E Population. Only the subset of participants who had a complete or partial intracranial response was included in this analysis.
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 30 24
Median (95% Confidence Interval)
Unit of Measure: weeks
24.1
(16.1 to 30.3)
28.1
(24.1 to 44.1)
6.Secondary Outcome
Title Duration of Intracranial Response for the Subset of V600K Mutation-positive Participants
Hide Description Duration of Intracranial Response is defined as the time from the first documented evidence of intracranial CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) until the time of the first documented intracranial disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).
Time Frame Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 31 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600K Population. Only the subset of participants who had a complete or partial intracranial response was included in this analysis.
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 1 4
Median (95% Confidence Interval)
Unit of Measure: weeks
12.4 [1] 
(NA to NA)
NA [2] 
(16.6 to NA)
[1]
The confidence interval cannot be calculated because too few participants were V600K mutation positive.
[2]
The median and the upper limit of the confidence interval cannot be calculated because too few V600K participants had intracranial responses.
7.Secondary Outcome
Title Duration of Overall Response for the Subset of V600E Mutation-positive Participants
Hide Description Duration of Overall Response is defined as the time from the first documented evidence of overall CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) until the time of the first documented disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).
Time Frame Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 28 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600E Population. Only the subset of participants who had a complete or partial response was included in this analysis.
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 30 23
Median (95% Confidence Interval)
Unit of Measure: weeks
27.6
(16.6 to 32.4)
23.7
(20.0 to 28.1)
8.Secondary Outcome
Title Duration of Overall Response for the Subset of V600K Mutation-positive Participants
Hide Description Duration of Overall Response is defined as the time from the first documented evidence of overall CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]) until the time of the first documented disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm).
Time Frame Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 31 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600K Population. Only the subset of participants who had a complete or partial response was included in this analysis.
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 0 5
Median (95% Confidence Interval)
Unit of Measure: weeks
36.1 [1] 
(12.3 to NA)
[1]
The upper limit of the confidence interval cannot be calculated because too few V600K participants had intracranial responses.
9.Secondary Outcome
Title Progression-free Survival in V600E Mutation-positive Participants
Hide Description PFS is defined as the time from the first dose of study medication to the earliest of death or progression (at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). If a participant received subsequent anti-cancer therapy prior to the date of documented PD/death, the participant was censored at the last adequate assessment and the visit level response was CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters [e.g., percent change from Baseline]), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame Time from the first dose of study medication to the earliest of death or progression (average of 23 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600E Population
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 74 65
Median (95% Confidence Interval)
Unit of Measure: weeks
16.1
(15.7 to 23.4)
16.0
(15.9 to 23.9)
10.Secondary Outcome
Title Progression-free Survival in V600K Mutation-positive Participants
Hide Description PFS is defined as the time from the first dose of study medication to the earliest of death or progression (at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). If a participant received subsequent anti-cancer therapy prior to the date of documented PD/death, the participant was censored at the last adequate assessment and the visit level response was CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters [e.g., percent change from Baseline]), or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame Time from the first dose of study medication to the earliest of death or progression (average of 17 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600K Population
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 15 18
Median (95% Confidence Interval)
Unit of Measure: weeks
8.1
(3.1 to 16.1)
15.6
(7.9 to 17.6)
11.Secondary Outcome
Title Overall Survival of V600E Mutation-positive Participants
Hide Description Overall survival (OS) is defined as the time from the first dose of study medication until death due to any cause. OS was censored using the date of last known contact for those participants who were alive at the time of analysis.
Time Frame Time from the first dose of study medication until death due to any cause (average of 35 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600E Population
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 74 65
Median (95% Confidence Interval)
Unit of Measure: months
6.8
(6.1 to 9.2)
7.6
(6.3 to 10.6)
12.Secondary Outcome
Title Overall Survival in V600K Mutation-positive Participants
Hide Description Overall survival (OS) is defined as the time from the first dose of study medication until death due to any cause. OS was censored using the date of last known contact for those participants who were alive at the time of analysis.
Time Frame Time from the first dose of study medication until death due to any cause (average of 26 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
V600K Population
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 15 18
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(1.6 to 5.2)
5.0
(3.1 to 11.9)
13.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.
Time Frame From Screening until the conclusion of the study (up to 103 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Subjects (ATS) Population: all participants who received at least one dose of study treatment
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 89 83
Measure Type: Number
Unit of Measure: participants
Any AE 81 79
Any SAE 26 31
14.Secondary Outcome
Title Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters
Hide Description Clinical chemistry data were summarized at each scheduled assessment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade (G) 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life threatening; Grade 5, death related to toxicity. Blood sample was collected for the assessment of glucose, potassium, magnesium, sodium, phosphorus, potassium. aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, total bilirubin, albumin, amylase, cholesterol, creatine kinase, gamma glutamyl transferase (GGT), lipase, blood pH, and triglycerides.
Time Frame From Screening until the conclusion of the study (up to 103 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants with data available for the indicated parameters were analyzed.
Arm/Group Title GSK2118436 150 mg
Hide Arm/Group Description:
Participants with or without prior local therapy for brain metastasis received GSK2118436 50 mg and 75 mg capsules either one hour before or 2 hours after a meal twice daily.
Overall Number of Participants Analyzed 165
Measure Type: Number
Unit of Measure: participants
Glucose (hyperglycemia), AGI, n=165 71
Glucose (hyperglycemia), Increase to G 3, n=165 8
Glucose (hyperglycemia), Increase to G 4, n=165 1
Glucose (hypoglycemia), AGI, n=165 24
Glucose (hypoglycemia), Increase to G 3, n=165 0
Glucose (hypoglycemia), Increase to G 4, n=165 0
Magnesium (hypermagnesemia) AGI, n=165 2
Magnesium (hypermagnesemia), Increase to G 3,n=165 0
Magnesium (hypermagnesemia), Increase to G 4,n=165 0
Magnesium (hypomagnesemia), AGI, n=165 0
Magnesium (hypomagnesemia), Increase to G 3, n=165 0
Magnesium (hypomagnesemia), Increase to G 4, n=165 0
Sodium (hypernatremia), AGI, n=165 8
Sodium (hypernatremia), Increase to G 3, n=165 0
Sodium (hypernatremia), Increase to G 4, n=165 0
Sodium (hyponatremia), AGI, n=165 21
Sodium (hyponatremia), Increase to G 3, n=165 3
Sodium (hyponatremia), Increase to G. 4, n=165 0
Phosphorus inorganic, AGI, n=165 53
Phosphorus inorganic, Increase to G 3, n=165 13
Phosphorus inorganic, Increase to G 4, n=165 0
Potassium (hyperkalemia), AGI, n=165 8
Potassium (hyperkalemia), Increase to G 3, n=165 0
Potassium (hyperkalemia), Increase to G 4, n=165 0
Potassium (hypokalemia), AGI, n=165 17
Potassium (hypokalemia), Increase to G 3, n=165 4
Potassium (hypokalemia), Increase to G 4, n=165 0
ALP, AGI, n=165 41
ALP, Increase to G 3, n=165 1
ALP, Increase to G 4, n=165 0
AST, AGI, n=165 26
AST, Increase to G 3, n=165 1
AST, Increase to G 4, n=165 0
ALT, AGI, n=165 27
ALT, Increase to G 3, n=165 2
ALT, Increase to G 4, n=165 0
Creatinine, AGI, n=165 10
Creatinine, Increase to G 3, n=165 0
Creatinine, Increase to G 4, n=165 0
Total bilirubin, AGI, n=163 5
Total bilirubin, Increase to G 3 n=163 0
Total bilirubin, Increase to G 4 n=163 0
Albumin, AGI, n=27 9
Albumin, Increase to G 3, n=27 0
Albumin, Increase to G 4, n=27 0
Amylase, AGI, n=16 3
Amylase, Increase to G 3, n=16 1
Amylase, Increase to G 4, n=16 1
Cholesterol, AGI, n=2 1
Cholesterol, Increase to G 3, n=2 0
Cholesterol, Increase to G 4, n=2 0
Creatine kinase, AGI, n=6 1
Creatine kinase, Increase to G 3, n=6 0
Creatine kinase, Increase to G 4, n=6 1
GGT, AGI, n=22 13
GGT, Increase to G 3, n=22 4
GGT, Increase to G 4, n=22 0
Lipase, AGI, n=19 10
Lipase, Increase to G 3, n=19 4
Lipase, Increase to G 4, n=19 2
Blood pH, AGI, n=1 0
Blood pH, Increase to G 3, n=1 0
Blood pH, Increase to G 4, n=1 0
Triglycerides, AGI, n=5 3
Triglycerides, Increase to G 3, n=5 0
Triglycerides, Increase to G 4, n=5 0
15.Secondary Outcome
Title Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities
Hide Description Blood samples were collected for the assessment of hepatobiliary parameters. ALT=alanine aminotranserase; AST=aspartate aminotransferase; ALP=alkaline phosphatase; BIL=total bilirubin; INR=international normalized ratio; ULN=upper limit of normal. Hepato-cellular injury is defined as (ALT/ULN)/(ALP/ULN) >=5.
Time Frame From Screening until the conclusion of the study (up to 103 weeks)
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ATS Population
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 89 83
Measure Type: Number
Unit of Measure: participants
Possible HYs Law, >3x ULN ALT, >=2x ULN BIL 0 0
Possible HYs Law, >3x ULN ALT, >1.5x ULN INR 0 0
Hepato-cellular injury 2 1
Bilirubin elevations, >=2x ULN BIL 0 1
Bilirubin elevations, >=2x ULN BIL and <2x ULN BIL 0 1
ALT or AST elevations, >3x ULN ALT or AST 2 4
ALT or AST elevations, >5x ULN ALT or AST 1 1
ALT or AST elevations, >8x ULN ALT or AST 1 1
ALT or AST elevations, >20x ULN ALT or AST 0 0
ALT elevations, >3x ULN ALT 2 4
ALT elevations, >5x ULN ALT 1 1
ALT elevations, >8x ULN ALT 1 1
ALT elevations, >20x ULN ALT 0 0
ALT elevations, >3x ULN ALT, <=3x ULN ALT Baseline 2 4
ALP elevations, >=3x ULN ALP 5 2
ALP elevations, >=3x ULN ALP and <3x ULN ALP 4 2
16.Secondary Outcome
Title Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters
Hide Description Hematology data were summarized at each scheduled assessment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Grade refers to the severity of the toxicity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1, mild; Grade 2, moderate; Grade 3, severe, Grade 4, life threatening, Grade 5, death related to toxicity. Blood sample was collected for the assessment of hemoglobin, white blood cells, and platelet count.
Time Frame From Screening until the conclusion of the study (up to 103 weeks)
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ATS Population. Only those participants with data available for the indicated parameters were analyzed.
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 84 81
Measure Type: Number
Unit of Measure: participants
Hemoglobin (anemia), AGI 25 81
Hemoglobin (anemia), Increase to Grade 3 2 3
Hemoglobin (anemia), Increase to Grade 4 0 0
Hemoglobin (increased), AGI 1 0
Hemoglobin (increased), Increase to Grade 3 0 0
Hemoglobin (increased), Increase to Grade 4 0 0
Lymphocyte count increased, AGI 0 0
Lymphocyte count increased, Increase to Grade 3 0 0
Lymphocyte count increased, Increase to Grade 4 0 0
Lymphocyte count decreased, AGI 18 81
Lymphocyte count decreased, Increase Grade 3 4 6
Lymphocyte count decreased, Increase Grade 4 1 0
Total neutrophils, AGI, 6 11
Total neutrophils, Increase to Grade 3 0 0
Total neutrophils, Increase to Grade 4 2 2
Platelet count, AGI 7 9
Platelet count, Increase to Grade 3 2 1
Platelet count, Increase to Grade 4 1 0
White blood cell count, AGI 9 16
White blood cell count, Increase to Grade 3 0 0
White blood cell count, Increase to Grade 4 1 1
17.Secondary Outcome
Title Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36
Hide Description Systolic and diastolic blood pressure were measured for all treated participants.
Time Frame Baseline; Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36
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Hide Analysis Population Description
ATS Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 89 83
Mean (Standard Deviation)
Unit of Measure: millimeters of mercury (mmHg)
Diastolic BP, Baseline, n=89,83 77.7  (8.78) 77.1  (9.73)
Diastolic BP, Week 4, n=81, 78 74.0  (10.12) 74.6  (10.88)
Diastolic BP, Week 8, n=70, 73 74.6  (9.14) 72.7  (9.54)
Diastolic BP, Week 12, n=68, 62 75.2  (7.70) 74.3  (11.64)
Diastolic BP, Week 16, n=52, 52 73.2  (10.01) 71.4  (9.40)
Diastolic BP, Week 20, n=29, 34 73.6  (9.98) 71.7  (9.67)
Diastolic BP, Week 24, n=22, 25 74.7  (7.87) 72.7  (9.99)
Diastolic BP, Week 28, n=15, 17 73.9  (6.98) 76.5  (8.37)
Diastolic BP, Week 32, n=9, 7 73.1  (9.47) 73.6  (9.64)
Diastolic BP, Week 36, n=2, 1 75.5  (7.78) 93.0 [1]   (NA)
Systolic BP, Baseline, n=89, 83 126.6  (16.73) 123.9  (14.17)
Systolic BP, Week 4, n=81, 78 122.2  (13.68) 121.9  (15.37)
Systolic BP, Week 8, n=70, 73 123.0  (12.71) 117.3  (14.53)
Systolic BP, Week 12, 68, 62 123.6  (14.74) 120.1  (14.21)
Systolic BP, Week 16, n=52, 52 124.7  (17.70) 119.9  (11.67)
Systolic BP, Week 20, n=29, 34 123.7  (16.02) 118.9  (13.51)
Systolic BP, Week 24, n=22, 25 126.3  (17.80) 120.9  (16.63)
Systolic BP, Week 28, n=15, 17 122.2  (17.03) 120.8  (14.32)
Systolic BP, Week 32, n=9, 7 122.8  (14.84) 117.7  (10.01)
Systolic BP, Week 36, n=2, 1 119.5  (13.44) 128.0 [1]   (NA)
[1]
Standard deviation could not be calculated because only one participant was analyzed in this treatment group at this time point.
18.Secondary Outcome
Title Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG)
Hide Description An increase in the QTc interval corrected using Bazett's formula (Bazett's QTc) was recorded for all treated participants. Grade 1 (450-480 milliseconds [msec]), Grade 2 (481-500 msec), Grade 3/4 (>=501 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade.
Time Frame Baseline; Weeks 4, 12, 20, 28, 40, 52, and 64
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Hide Analysis Population Description
ATS Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 75 74
Measure Type: Number
Unit of Measure: participants
Increase from Baseline to any grade 11 17
Increase from Baseline to Grade 2 1 2
Increase from Baseline to Grade 3/4 0 0
19.Secondary Outcome
Title Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12
Hide Description Echocardiograms (ECHO) were measured for all treated participants. An echocardiogram test gives information about the structure and function of the heart. LLN=lower limit of normal (determined by the institution).
Time Frame Weeks (W) 4 and 12
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ATS Population
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 89 83
Measure Type: Number
Unit of Measure: participants
W 4, Left ventricle (LV) ejection fraction < LLN 1 0
W 4, LV ejection fraction < normal 0 0
W 12, LV ejection fraction < LLN 0 0
W 12, LV ejection fraction < normal 1 0
20.Secondary Outcome
Title Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542
Hide Description Summary statistics were calculated for each time point by cohort. The population pharmacokinetics were determined using a non-linear mixed effects modeling approach after pooling the data with other studies. These results are reported separately.
Time Frame Week 4 (pre-dose and 1-3 hours post-dose) and Weeks 8, 16, 24, and 32 (either pre-dose in the morning or in the afternoon at 4-8 hours post-dose)
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PK Population: participants in the ATS population for whom a PK sample was obtained and analyzed. Only those participants whose samples were available at the indicated time points were analyzed.
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 75 77
Median (Full Range)
Unit of Measure: nanograms per milliliter (ng/mL)
GSK2118436, Week 4, predose, n=55, 58
31.6
(7 to 2995)
50.2
(0 to 4293)
GSK2118436, Week 4, 1-3 hours (hrs), n=63, 70
992.1
(5 to 4870)
810.7
(4 to 4995)
GSK2118436, Week 8, predose, n=36, 36
27.2
(8 to 1148)
37.5
(3 to 944)
GSK2118436, Week 8, 4-8 hrs, n=19, 25
274.7
(28 to 1062)
294.5
(15 to 2011)
GSK2118436, Week 16, predose, n=26, 23
27.8
(6 to 3390)
30.7
(3 to 203)
GSK2118436, Week 16, 4-8 hrs, n=11, 18
341.5
(33 to 1141)
295.8
(55 to 1808)
GSK2118436, Week 24, predose, n=14, 10
60.7
(1 to 597)
53.8
(14 to 211)
GSK2118436, Week 24, 4-8 hrs, n=5, 12
371.2
(0 to 1072)
226.1
(30 to 974)
GSK2118436, Week 32, predose, n=11, 7
38.6
(7 to 777126)
28.4
(2 to 87)
GSK2118436, Week 32, 4-8 hrs, n=2, 8
227.6
(90 to 365)
335.7
(94 to 1939)
GSK2285403, Week 4, predose, n=55, 58
62.7
(9 to 1495)
80.5
(0 to 2931)
GSK2285403, Week 4, 1-3 hrs, n=63, 70
688.9
(15 to 2499)
593.2
(8 to 2812)
GSK2285403, Week 8, predose, n=36, 36
46.5
(10 to 1743)
74.4
(6 to 553)
GSK2285403, Week 8, 4-8 hrs, n=19, 25
335.5
(55 to 1114)
310.5
(12 to 3160)
GSK2285403, Week 16, predose, n=26, 23
45.1
(10 to 824)
54.4
(5 to 354)
GSK2285403, Week 16, 4-8 hrs, n=11, 18
434.1
(44 to 976)
456.9
(148 to 1053)
GSK2285403, Week 24, predose, n=14, 10
97.3
(6 to 386)
103.3
(14 to 325)
GSK2285403, Week 24, 4-8 hrs, n=5, 12
617.1
(0 to 1057)
357.7
(79 to 959)
GSK2285403, Week 32, predose, n=11, 7
63.1
(8 to 934)
46.6
(4 to 88)
GSK2285403, Week 32, 4-8 hrs, n=2, 8
375.3
(118 to 633)
377.5
(117 to 1519)
GSK2298683, Week 4, predose, n=55, 58
3215.8
(1225 to 14064)
3877.4
(43 to 13435)
GSK2298683, Week 4, 1-3 hrs, n=63, 70
4272.5
(747 to 18161)
4500.3
(275 to 18196)
GSK2298683, Week 8, predose, n=36, 36
3152.0
(1564 to 10402)
3250.0
(667 to 12747)
GSK2298683, Week 8, 4-8 hrs, n=19, 25
4692.1
(2133 to 11320)
5447.5
(2015 to 15009)
GSK2298683, Week 16, predose, n=26, 23
3070.0
(1143 to 11414)
3561.2
(922 to 10204)
GSK2298683, Week 16, 4-8 hrs, n=11, 18
4865.5
(2670 to 11821)
6595.7
(1630 to 11380)
GSK2298683, Week 24, predose, n=14, 10
3026.8
(1532 to 14762)
4199.7
(2040 to 7504)
GSK2298683, Week 24, 4-8 hrs, n=5, 12
3825.9
(320 to 13056)
5659.9
(3225 to 11009)
GSK2298683, Week 32, predose, n=11, 7
2386.6
(1421 to 6528)
2451.7
(1253 to 5026)
GSK2298683, Week 32, 4-8 hrs, n=2, 8
11225.8
(5323 to 17129)
6547.4
(4578 to 8786)
GSK2167542, Week 4, predose, n=55, 58
317.9
(50 to 1338)
323.0
(3 to 2690)
GSK2167542, Week 4, 1-3 hrs, n=63, 70
351.6
(62 to 1505)
332.1
(46 to 1619)
GSK2167542, Week 8, predose, n=36, 36
324.1
(86 to 964)
298.6
(56 to 1272)
GSK2167542, Week 8, 4-8 hrs, n=19, 25
305.4
(91 to 899)
320.5
(78 to 960)
GSK2167542, Week 16, predose, n=26, 23
285.5
(93 to 1095)
310.8
(35 to 1200)
GSK2167542, Week 16, 4-8 hrs, n=11, 18
291.1
(69 to 769)
320.5
(81 to 652)
GSK2167542, Week 24, predose, n=14, 10
304.0
(94 to 875)
334.0
(63 to 795)
GSK2167542, Week 24, 4-8 hrs, n=5, 12
190.7
(19 to 401)
287.9
(106 to 599)
GSK2167542, Week 32, predose, n=11, 2
361.2
(113 to 960)
316.3
(69 to 690)
GSK2167542, Week 32, 4-8 hrs, n=2, 8
227.8
(225 to 231)
273.9
(231 to 1021)
21.Secondary Outcome
Title Composite of Pharmacokinetic Parameters of GSK2118436 in a Subset of Participants Receiving Dexamethasone
Hide Description This outcome measure could not be analyzed because too few participants participated in the dexamethasone study.
Time Frame Day 15
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[Not Specified]
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description:
Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
22.Secondary Outcome
Title Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response
Hide Description The BRAF screening assay determines the specific BRAF mutational status (V600 E and K) in participants with metastatic melanoma who may benefit from treatment with GSK2118436. Per RECIST, version 1.1, CR is defined as the disappearance of all lesions. PR is defined as a >=30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline (BL) sum of the diameters (e.g., percent change from BL). Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD is defined as a >=20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir [smallest sum of diameters recorded since treatment start]). In addition, the sum must have an absolute increase from nadir of 5 millimeters. Not evaluable: cannot be classified by a preceding definition.
Time Frame Screening
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V600EK and THIDEK Population: all enrolled participants who were V600E or V600K mutation positive by the RGI IUO assay
Arm/Group Title RGI IUO Mutation Positive Participants ThxID BRAF Mutation Positive Participants
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Melanoma participants determined to be positive for the BRAF V600E and V600K mutations as determined by the RGI assay. The RGI assay is a BRAF mutation test developed by Response Genetics Incorporated, and was used to determine eligibility. It employs the allele-specific polymerase chain reaction (ASPCR) methodology, and was offered as an Investigational Use Only assay (only for pre-market investigational purposes).
Melanoma participants determined to be positive for the BRAF V600E and V600K mutations as determined by the ThxID assay. The RGI test was further validated by BioMerieux (BMX THxID assay) for regulatory approval. The THxID IUO assay was used to retrospectively confirm the RGI test results.
Overall Number of Participants Analyzed 172 155
Measure Type: Number
Unit of Measure: participants
Complete response 2 2
Partial response 52 49
Stable disease 78 69
Progressive disease 26 23
Not evaluable 14 12
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the time the first dose of study treatment was administered until 30 days following discontinuation of study treatment (up to 103 weeks).
Adverse Event Reporting Description SAEs and non-serious AEs were collected in the All Treated Subjects (ATS) Population, comprised of all participants who received at least one dose of study medication.
 
Arm/Group Title GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Hide Arm/Group Description Participants who received no prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events. Participants who received prior local therapy for brain metastasis received GSK2118436 150 mg capsules either one hour before or 2 hours after a meal twice daily until evidence of disease progression, death, or unacceptable adverse events.
All-Cause Mortality
GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   26/89 (29.21%)   31/83 (37.35%) 
Blood and lymphatic system disorders     
Neutropenia  1  2/89 (2.25%)  0/83 (0.00%) 
Pancytopenia  1  0/89 (0.00%)  2/83 (2.41%) 
Agranulocytosis  1  0/89 (0.00%)  1/83 (1.20%) 
Anaemia  1  0/89 (0.00%)  1/83 (1.20%) 
Disseminated intravascular coagulation  1  0/89 (0.00%)  1/83 (1.20%) 
Leukopenia  1  1/89 (1.12%)  0/83 (0.00%) 
Thrombocytopenia  1  1/89 (1.12%)  0/83 (0.00%) 
Cardiac disorders     
Atrial fibrillation  1  2/89 (2.25%)  0/83 (0.00%) 
Atrial flutter  1  1/89 (1.12%)  0/83 (0.00%) 
Cardiac arrest  1  1/89 (1.12%)  0/83 (0.00%) 
Gastrointestinal disorders     
Pyrexia  1  4/89 (4.49%)  9/83 (10.84%) 
Nausea  1  1/89 (1.12%)  1/83 (1.20%) 
Vomiting  1  0/89 (0.00%)  2/83 (2.41%) 
Pancreatitis  1  1/89 (1.12%)  0/83 (0.00%) 
Subileus  1  1/89 (1.12%)  0/83 (0.00%) 
General disorders     
Chills  1  1/89 (1.12%)  2/83 (2.41%) 
Fatigue  1  0/89 (0.00%)  2/83 (2.41%) 
Influenza like illness  1  0/89 (0.00%)  1/83 (1.20%) 
Oedema peripheral  1  1/89 (1.12%)  0/83 (0.00%) 
Pain  1  1/89 (1.12%)  0/83 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  0/89 (0.00%)  1/83 (1.20%) 
Infections and infestations     
Infection  1  1/89 (1.12%)  0/83 (0.00%) 
Pneumonia  1  0/89 (0.00%)  1/83 (1.20%) 
Viral pericarditis  1  1/89 (1.12%)  0/83 (0.00%) 
Cellulitis  1  1/89 (1.12%)  0/83 (0.00%) 
Urinary tract infection  1  1/89 (1.12%)  0/83 (0.00%) 
Injury, poisoning and procedural complications     
Femoral neck fracture  1  1/89 (1.12%)  0/83 (0.00%) 
Investigations     
Ejection fraction decreased  1  3/89 (3.37%)  0/83 (0.00%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  0/89 (0.00%)  1/83 (1.20%) 
Musculoskeletal and connective tissue disorders     
Arthritis  1  1/89 (1.12%)  0/83 (0.00%) 
Bone pain  1  0/89 (0.00%)  1/83 (1.20%) 
Mobility decreased  1  0/89 (0.00%)  1/83 (1.20%) 
Muscular weakness  1  0/89 (0.00%)  1/83 (1.20%) 
Pain in extremity  1  0/89 (0.00%)  1/83 (1.20%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Squamous cell carcinoma  1  6/89 (6.74%)  7/83 (8.43%) 
Bowen's disease  1  0/89 (0.00%)  1/83 (1.20%) 
Metastases to meninges  1  1/89 (1.12%)  0/83 (0.00%) 
Nervous system disorders     
Haemorrhage intracranial  1  2/89 (2.25%)  3/83 (3.61%) 
Headache  1  2/89 (2.25%)  2/83 (2.41%) 
Syncope  1  1/89 (1.12%)  1/83 (1.20%) 
Aphasia  1  1/89 (1.12%)  0/83 (0.00%) 
Cerebrovascular accident  1  0/89 (0.00%)  1/83 (1.20%) 
Convulsion  1  0/89 (0.00%)  2/83 (2.41%) 
Depressed level of consciousness  1  0/89 (0.00%)  1/83 (1.20%) 
Dizziness  1  0/89 (0.00%)  1/83 (1.20%) 
Hemiparesis  1  0/89 (0.00%)  1/83 (1.20%) 
Lethargy  1  0/89 (0.00%)  1/83 (1.20%) 
Motor dysfunction  1  1/89 (1.12%)  0/83 (0.00%) 
Paraesthesia  1  0/89 (0.00%)  1/83 (1.20%) 
Partial seizures  1  1/89 (1.12%)  1/83 (1.20%) 
Somnolence  1  0/89 (0.00%)  1/83 (1.20%) 
Cerebral haemorrhage  1  2/89 (2.25%)  1/83 (1.20%) 
Intracranial tumour haemorrhage  1  1/89 (1.12%)  1/83 (1.20%) 
Psychiatric disorders     
Mental status changes  1  0/89 (0.00%)  1/83 (1.20%) 
Renal and urinary disorders     
Renal failure  1  1/89 (1.12%)  0/83 (0.00%) 
Renal failure acute  1  1/89 (1.12%)  1/83 (1.20%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/89 (0.00%)  1/83 (1.20%) 
Pleural effusion  1  1/89 (1.12%)  0/83 (0.00%) 
Pulmonary embolism  1  2/89 (2.25%)  0/83 (0.00%) 
Vascular disorders     
Hypotension  1  0/89 (0.00%)  3/83 (3.61%) 
Deep vein thrombosis  1  0/89 (0.00%)  1/83 (1.20%) 
Thrombosis  1  0/89 (0.00%)  1/83 (1.20%) 
Phlebitis  1  1/89 (1.12%)  0/83 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GSK2118436 150 mg: No Prior Local Therapy GSK2118436 150 mg: Prior Local Therapy
Affected / at Risk (%) Affected / at Risk (%)
Total   79/89 (88.76%)   74/83 (89.16%) 
Blood and lymphatic system disorders     
Anaemia  1  6/89 (6.74%)  4/83 (4.82%) 
Lymphopenia  1  3/89 (3.37%)  5/83 (6.02%) 
Gastrointestinal disorders     
Nausea  1  16/89 (17.98%)  26/83 (31.33%) 
Vomiting  1  18/89 (20.22%)  15/83 (18.07%) 
Diarrhoea  1  7/89 (7.87%)  15/83 (18.07%) 
Constipation  1  3/89 (3.37%)  11/83 (13.25%) 
Abdominal pain  1  6/89 (6.74%)  3/83 (3.61%) 
General disorders     
Pyrexia  1  23/89 (25.84%)  15/83 (18.07%) 
Fatigue  1  18/89 (20.22%)  25/83 (30.12%) 
Chills  1  9/89 (10.11%)  8/83 (9.64%) 
Oedema peripheral  1  5/89 (5.62%)  4/83 (4.82%) 
Asthenia  1  2/89 (2.25%)  6/83 (7.23%) 
Infections and infestations     
Nasopharyngitis  1  5/89 (5.62%)  2/83 (2.41%) 
Investigations     
Alanine aminotransferase increased  1  6/89 (6.74%)  4/83 (4.82%) 
Metabolism and nutrition disorders     
Decreased appetite  1  8/89 (8.99%)  13/83 (15.66%) 
Hypophosphataemia  1  5/89 (5.62%)  4/83 (4.82%) 
Hyperglycaemia  1  5/89 (5.62%)  3/83 (3.61%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  17/89 (19.10%)  13/83 (15.66%) 
Myalgia  1  12/89 (13.48%)  13/83 (15.66%) 
Pain in extremity  1  12/89 (13.48%)  8/83 (9.64%) 
Muscular weakness  1  4/89 (4.49%)  5/83 (6.02%) 
Back pain  1  2/89 (2.25%)  5/83 (6.02%) 
Musculoskeletal pain  1  2/89 (2.25%)  5/83 (6.02%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin papilloma  1  17/89 (19.10%)  8/83 (9.64%) 
Seborrhoeic keratosis  1  8/89 (8.99%)  7/83 (8.43%) 
Melanocytic naevus  1  8/89 (8.99%)  4/83 (4.82%) 
Acrochordon  1  7/89 (7.87%)  4/83 (4.82%) 
Dysplastic naevus  1  5/89 (5.62%)  2/83 (2.41%) 
Nervous system disorders     
Headache  1  24/89 (26.97%)  20/83 (24.10%) 
Dizziness  1  5/89 (5.62%)  3/83 (3.61%) 
Psychiatric disorders     
Insomnia  1  6/89 (6.74%)  6/83 (7.23%) 
Confusional state  1  0/89 (0.00%)  7/83 (8.43%) 
Depression  1  0/89 (0.00%)  5/83 (6.02%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  13/89 (14.61%)  5/83 (6.02%) 
Skin and subcutaneous tissue disorders     
Hyperkeratosis  1  24/89 (26.97%)  20/83 (24.10%) 
Rash  1  16/89 (17.98%)  14/83 (16.87%) 
Alopecia  1  15/89 (16.85%)  10/83 (12.05%) 
Palmar-plantar erythrodysaesthesia syndrome  1  15/89 (16.85%)  10/83 (12.05%) 
Dry skin  1  9/89 (10.11%)  4/83 (4.82%) 
Actinic keratosis  1  3/89 (3.37%)  6/83 (7.23%) 
Pruritus  1  7/89 (7.87%)  2/83 (2.41%) 
Dermatitis acneiform  1  5/89 (5.62%)  3/83 (3.61%) 
Transient acantholytic dermatosis  1  1/89 (1.12%)  6/83 (7.23%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01266967    
Other Study ID Numbers: 113929
First Submitted: December 2, 2010
First Posted: December 24, 2010
Results First Submitted: June 24, 2013
Results First Posted: March 5, 2014
Last Update Posted: May 8, 2014