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Trial record 16 of 510 for:    melanoma phase III

GSK1120212 vs Chemotherapy in Advanced or Metastatic BRAF V600E/K Mutation-positive Melanoma

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ClinicalTrials.gov Identifier: NCT01245062
Recruitment Status : Completed
First Posted : November 22, 2010
Results First Posted : March 15, 2013
Last Update Posted : April 5, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Interventions Drug: GSK1120212
Drug: Chemotherapy
Enrollment 322
Recruitment Details This was a randomized open-label, multi-center Phase III study to evaluate the efficacy and safety of single agent trametinib compared with chemotherapy (CT) (dacarbazine or paclitaxel). Participants (par.) were enrolled by 86 sites in 19 countries from December 2010 to July 2011. Results as of 16 December 2016 data-cut have been presented.
Pre-assignment Details Participants (par.) were stratified for lactate dehydrogenase and prior CT for advanced or metastatic disease. 1059 par. were screened and 322 were enrolled to receive trametinib (214 par.) or CT (108 par.) until disease progression, death, or withdrawal. Par. randomized to CT were allowed to cross-over to trametinib if disease progressed.
Arm/Group Title Trametinib Chemotherapy Cross-over From Chemotherapy to Trametinib
Hide Arm/Group Description Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal. Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. Participants randomized to chemotherapy and who did not receive subsequent anti-cancer therapy after discontinuing chemotherapy were allowed to cross-over to Trametinib and received 2 mg tablet once daily until disease progression, death or withdrawal.
Period Title: Randomization and Crossover Phase
Started [1] 214 108 0
Completed [2] 173 77 0
Not Completed 41 31 0
Reason Not Completed
Lost to Follow-up             4             2             0
Physician Decision             2             4             0
Withdrew Consent             12             11             0
Study closed/ terminated             23             14             0
[1]
Par. randomized onto study.
[2]
Par. completed the study as they died during the conduct of the study.
Period Title: Cross-over Phase
Started 0 0 70 [1]
Completed [2] 0 0 53
Not Completed 0 0 17
Reason Not Completed
Lost to Follow-up             0             0             1
Physician Decision             0             0             1
Withdrew Consent             0             0             4
Study closed/ terminated             0             0             11
[1]
As of the data cut on December 16, 2016, 70 of 108 participants crossed over from CT to trametinib.
[2]
Par. completed the study as they died during the conduct of the study.
Arm/Group Title Trametinib Chemotherapy Total
Hide Arm/Group Description Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal. Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. Total of all reporting groups
Overall Number of Baseline Participants 214 108 322
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 214 participants 108 participants 322 participants
54.3  (12.97) 52.8  (13.56) 53.8  (13.17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 214 participants 108 participants 322 participants
Female
94
  43.9%
55
  50.9%
149
  46.3%
Male
120
  56.1%
53
  49.1%
173
  53.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race/Ethnicity, Customized Number Analyzed 214 participants 108 participants 322 participants
White - Arabic/North African Heritage
2
   0.9%
0
   0.0%
2
   0.6%
White - White/Caucasian/European Heritage
212
  99.1%
107
  99.1%
319
  99.1%
White - Mixed Race
0
   0.0%
1
   0.9%
1
   0.3%
1.Primary Outcome
Title Progression-free Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases as Assessed by the Investigator and Independent Review
Hide Description Progression-free survival (PFS) is defined as the time from randomization to the first documented occurrence of disease progression (PD) or death. PFS for investigator-assessed and blinded, independent, central review committee (BRIC)-assessed responses was summarized per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, which is a set of published rules defining when cancer participants improve (respond), stay the same (stabilize), or worsen (progress) during treatment. Disease progression is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. Primary Efficacy Population included all participants with BRAF V600E mutation-positive melanoma without a history of brain metastases.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 178 95
Median (95% Confidence Interval)
Unit of Measure: Months
Investigator-Assessed
4.8
(3.5 to 4.9)
1.4
(1.4 to 2.7)
Independent Review
4.9
(4.5 to 5.1)
1.6
(1.4 to 2.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Trametinib, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from a stratified log-rank test was adjusted for prior chemotherapy for advanced or metastatic disease and Baseline lactate dehydrogenase.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.31 to 0.64
Estimation Comments Investigator-Assessed PFS. HR <1 indicates a lower risk with Trametinib compared with CT. HR from a stratified log-rank test was adjusted for prior chemotherapy for advanced or metastatic disease and Baseline lactate dehydrogenase.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Trametinib, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value from a stratified log-rank test was adjusted for prior chemotherapy for advanced or metastatic disease and Baseline lactate dehydrogenase.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.29 to 0.60
Estimation Comments Independent Review PFS. HR <1 indicates a lower risk with Trametinib compared with CT. HR from a stratified log-rank test was adjusted for prior chemotherapy for advanced or metastatic disease and Baseline lactate dehydrogenase.
2.Secondary Outcome
Title Progression-free Survival in All Participants
Hide Description PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death. Investigator-assessed and BRIC-assessed PFS were summarized per RECIST, Version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation. Intend-To-Treat (ITT) Population included all randomized participants regardless of whether or not treatment was administered.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 214 108
Median (95% Confidence Interval)
Unit of Measure: Months
Investigator-Assessed
4.9
(4.5 to 5.0)
1.5
(1.4 to 2.8)
Independent radiologist assessed-Assessed
4.9
(4.6 to 5.0)
1.5
(1.4 to 2.8)
3.Secondary Outcome
Title PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and Without Prior Chemotherapy as Assessed by the Investigator
Hide Description PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death. Investigator-assessed PFS was summarized per RECIST, Version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 114 62
Median (95% Confidence Interval)
Unit of Measure: Months
4.8
(3.4 to 5.0)
1.4
(1.4 to 1.7)
4.Secondary Outcome
Title PFS in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases and With Prior Chemotherapy as Assessed by the Investigator
Hide Description PFS is defined as the time from the date of randomization to the first documented occurrence of PD or death. Investigator-assessed PFS was summarized per RECIST, Version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 64 33
Median (95% Confidence Interval)
Unit of Measure: Months
4.8
(2.9 to 4.9)
2.7
(1.4 to 2.9)
5.Secondary Outcome
Title Overall Survival in All Participants
Hide Description Overall survival was defined as the time from the date of randomization to the date of death due to any cause.
Time Frame Day 1 until death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 214 108
Median (95% Confidence Interval)
Unit of Measure: Months
15.6
(13.5 to 17.3)
11.3
(7.2 to 14.8)
6.Secondary Outcome
Title Overall Survival in BRAF V600E Mutation-positive Participants Without a History of Brain Metastases
Hide Description Overall survival was defined as the time from the date of randomization to the date of death due to any cause. NA indicates data was not available.
Time Frame Day 1 until death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 178 95
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [2] 
(6.8 to NA)
[1]
At the time of this report, there was limited follow-up for survival; therefore, the median and the confidence interval (CI) could not be estimated.
[2]
At the time of this report, there was limited follow-up for survival; therefore, the median and the upper limit (UL) of the CI could not be estimated.
7.Secondary Outcome
Title Number of BRAF V600E Mutation-positive Participants Without a History of Brain Metastases With Overall Response (OR) as Assessed by the Investigator and Independent Review
Hide Description OR is defined as the number of participants with evidence of complete response (CR; disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator and an independent review per RECIST, Version 1.1.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 178 95
Measure Type: Number
Unit of Measure: Participants
Investigator-Assessed: CR 4 0
Investigator-Assessed: PR 39 7
Independent Review: CR 0 0
Independent Review: PR 33 3
8.Secondary Outcome
Title Number of Participants With OR as Assessed by the Investigator and Independent Review
Hide Description OR is defined as the number of participants with evidence of complete response (disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or partial response (at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator and an independent review per RECIST, Version 1.1.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 214 108
Measure Type: Number
Unit of Measure: Participants
Investigator-Assessed: CR 8 2
Investigator-Assessed: PR 53 8
Independent Review: CR 0 1
Independent Review: PR 41 4
9.Secondary Outcome
Title Number of BRAF V600E Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator
Hide Description OR is defined as the number of participants with evidence of complete response (disappearance of all extranodal lesions. Any pathological lymph node must be less than 10 mm in the short axis) or partial response (at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator per RECIST, Version 1.1.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 184 97
Measure Type: Number
Unit of Measure: Participants
V600E Mutation, CR 4 0
V600E Mutation, PR 40 7
10.Secondary Outcome
Title Number of BRAF V600K Mutation-positive Participants Classified as Confirmed Responders (CR and PR) as Assessed by the Investigator
Hide Description OR is defined as the number of participants with evidence of complete response (CR; disappearance of all extranodal lesions. Any pathological lymph node must be less than 10 mm in the short axis) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator per RECIST, Version 1.1.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 29 11
Measure Type: Number
Unit of Measure: Participants
V600K Mutation, CR 0 0
V600K Mutation, PR 3 2
11.Secondary Outcome
Title Number of Participants With OR Following Cross-over to Trametinib
Hide Description OR is defined as the number of participants with evidence of CR (disappearance of all target lesions. Any pathological lymph node must be less than 10 millimeters in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) evaluated by the Investigator in participants following cross-over to Trametinib. The evaluation was carried out by the Investigator per RECIST, Version 1.1. Cross-over Population included the subset of participants who were randomized to CT and who elected to cross-over to Trametinib following disease progression on CT. Only participants who received at least one dose of Trametinib were included in this population.
Time Frame Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Cross-over Population
Arm/Group Title Cross-over From Chemotherapy to Trametinib
Hide Arm/Group Description:
Participants randomized to chemotherapy and who did not receive subsequent anti-cancer therapy after discontinuing chemotherapy were allowed to cross-over to Trametinib and received 2 mg tablet once daily until disease progression, death or withdrawal.
Overall Number of Participants Analyzed 70
Measure Type: Number
Unit of Measure: Participants
CR 2
PR 29
12.Secondary Outcome
Title Duration of Response (DoR) for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classified as Confirmed Responders (CR or PR) as Assessed by the Investigator Review
Hide Description DoR is defined as the time from the first documented evidence of CR (disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until PD (at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation) or death due to any cause. DoR for the investigator-assessed (INVA) response data were summarized per RECIST, Version 1.1. Only those participants with confirmed response (CR and PR) were analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data was not available.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 43 7
Median (95% Confidence Interval)
Unit of Measure: Months
5.5
(4.9 to 5.9)
NA [1] 
(3.5 to NA)
[1]
There were too few events to provide an estimable median or UL of the CI.
13.Secondary Outcome
Title DoR for All BRAF V600E Mutation-positive Participants Without a Prior History of Brain Metastases Classified as Confirmed Responders (CR or PR) as Assessed by the Independent Review
Hide Description DoR is defined as the time from the first documented evidence of CR (disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until PD (at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation) or death due to any cause. DoR for the independently-assessed (INDA) response data were summarized per RECIST, Version 1.1. Only those participants with confirmed response (CR and PR) were analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data was not available.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Efficacy Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 33 3
Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(3.8 to 5.9)
NA [1] 
(3.5 to NA)
[1]
There were too few events to provide an estimable median or UL of the CI.
14.Secondary Outcome
Title DoR for All Confirmed Responders (CR or PR) as Assessed by the Investigator Review
Hide Description DoR is defined as the time from the first documented evidence of CR (disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until 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 with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation. DoR for the INVA response data was summarized per RECIST, Version 1.1. Only those participants with confirmed response (CR and PR) were analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data was not available.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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ITT Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 47 9
Median (95% Confidence Interval)
Unit of Measure: Months
5.5
(4.1 to 5.9)
NA [1] 
(5.0 to NA)
[1]
There were too few events to provide an estimable median or UL of the CI.
15.Secondary Outcome
Title DoR for All Confirmed Responders (CR or PR) as Assessed by the Independent Review
Hide Description DoR is defined as the time from the first documented evidence of CR (disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until 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 with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation. DoR for the INDA response data was summarized per RECIST, Version 1.1. Only those participants with confirmed response (CR and PR) were analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data was not available.
Time Frame Day 1 until the earliest date of disease progression or death due to any cause (average of 20.3 months)
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Hide Analysis Population Description
ITT Population
Arm/Group Title Trametinib Chemotherapy
Hide Arm/Group Description:
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal.
Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal.
Overall Number of Participants Analyzed 41 5
Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(4.1 to 5.9)
NA [1] 
(5.0 to NA)
[1]
There were too few events to provide an estimable median or UL of the CI.
16.Secondary Outcome
Title DoR for All Responders (CR or PR) Following Cross-over to Trametinib as Assessed by the Investigator
Hide Description DoR is defined as the time from the first documented evidence of CR (disappearance of all extra nodal lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the diameters of target lesions) until 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 with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation. DoR data were summarized per RECIST, Version 1.1Only those participants with confirmed response (CR and PR) were analyzed. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates data was not available.
Time Frame Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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Cross-over Population
Arm/Group Title Cross-over From Chemotherapy to Trametinib
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Participants randomized to chemotherapy and who did not receive subsequent anti-cancer therapy after discontinuing chemotherapy were allowed to cross-over to Trametinib and received 2 mg tablet once daily until disease progression, death or withdrawal.
Overall Number of Participants Analyzed 13
Median (95% Confidence Interval)
Unit of Measure: Months
2.7 [1] 
(1.3 to NA)
[1]
There were too few events to provide an estimable UL of the CI.
17.Secondary Outcome
Title PFS Following Cross-over to Trametinib as Assessed by the Investigator
Hide Description PFS is defined as the time from the first dose of cross-over therapy to the first documented occurrence of PD or death. PFS was summarized per RECIST, Version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation.
Time Frame Day 1 of cross-over therapy until the earliest date of disease progression or death due to any cause (average of 18.3 months)
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Cross-over Population
Arm/Group Title Cross-over From Chemotherapy to Trametinib
Hide Arm/Group Description:
Participants randomized to chemotherapy and who did not receive subsequent anti-cancer therapy after discontinuing chemotherapy were allowed to cross-over to Trametinib and received 2 mg tablet once daily until disease progression, death or withdrawal.
Overall Number of Participants Analyzed 70
Median (95% Confidence Interval)
Unit of Measure: Months
3.0
(2.7 to 4.8)
Time Frame Participants were analyzed from the first dose of study medication to 28 days after discontinuation of study medication (average of 20.3 months in the Randomization Phase and 18.3 months in the Cross-over Phase).
Adverse Event Reporting Description Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all randomized participants included in the study who received at least one dose of study medication.
 
Arm/Group Title Trametinib Chemotherapy Cross-over From Chemotherapy to Trametinib
Hide Arm/Group Description Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF (a human gene encoding for protein called B-Raf, which is involved in a signaling pathway and is important for cell growth) V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received a Trametinib 2 milligram (mg) tablet once daily until disease progression, death, or withdrawal. Participants with histologically confirmed cutaneous advanced or metastatic melanoma (Stage IIIC or Stage IV), with a BRAF V600 E/K mutation-positive tumor sample as determined via the central BRAF mutation assay, received an intravenous (IV) dose of Dacarbazine 1000 mg per square meter every 3 weeks or Paclitaxel 175 mg per square meter every 3 weeks at the discretion of the investigator, provided the participant had not received that type of chemotherapy before randomization, until disease progression, death, or withdrawal. Participants randomized to chemotherapy and who did not receive subsequent anti-cancer therapy after discontinuing chemotherapy were allowed to cross-over to Trametinib and received 2 mg tablet once daily until disease progression, death or withdrawal.
All-Cause Mortality
Trametinib Chemotherapy Cross-over From Chemotherapy to Trametinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   172/211 (81.52%)   22/99 (22.22%)   53/70 (75.71%) 
Show Serious Adverse Events Hide Serious Adverse Events
Trametinib Chemotherapy Cross-over From Chemotherapy to Trametinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   52/211 (24.64%)   19/99 (19.19%)   18/70 (25.71%) 
Blood and lymphatic system disorders       
Anaemia  1  3/211 (1.42%)  2/99 (2.02%)  1/70 (1.43%) 
Leukopenia  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Pancytopenia  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Cardiac disorders       
Acute coronary syndrome  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Cardiac failure  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Conduction disorder  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Left ventricular dysfunction  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Myocardial infarction  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Pericarditis  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Eye disorders       
Eyelid ptosis  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Retinal vein occlusion  2  2/211 (0.95%)  0/99 (0.00%)  0/70 (0.00%) 
Gastrointestinal disorders       
Vomiting  1  3/211 (1.42%)  1/99 (1.01%)  1/70 (1.43%) 
Nausea  1  1/211 (0.47%)  1/99 (1.01%)  0/70 (0.00%) 
Constipation  1  1/211 (0.47%)  1/99 (1.01%)  0/70 (0.00%) 
Diarrhea  1  1/211 (0.47%)  1/99 (1.01%)  0/70 (0.00%) 
Dysphagia  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Gastric hemorrhage  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Colitis  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Gastritis  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Gastritis erosive  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Large intestinal ulcer  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
General disorders       
Pyrexia  1  3/211 (1.42%)  4/99 (4.04%)  2/70 (2.86%) 
Axillary pain  1  0/211 (0.00%)  1/99 (1.01%)  1/70 (1.43%) 
General physical health deterioration  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Edema  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Pain  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Death  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Oedema peripheral  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Hepatobiliary disorders       
Cholecystitis  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Cholangitis  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Gallbladder obstruction  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Hepatic failure  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Jaundice  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Immune system disorders       
Anaphylactic reaction  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Corneal graft rejection  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Hypersensitivity  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Infections and infestations       
Cellulitis  1  4/211 (1.90%)  0/99 (0.00%)  2/70 (2.86%) 
Erysipelas  1  5/211 (2.37%)  0/99 (0.00%)  1/70 (1.43%) 
Infection  1  2/211 (0.95%)  0/99 (0.00%)  0/70 (0.00%) 
Bronchitis  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Eye infection  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Klebsiella infection  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Localized infection  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Lymphangitis  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Pneumonia  1  1/211 (0.47%)  1/99 (1.01%)  0/70 (0.00%) 
Rash pustular  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Sepsis  1  1/211 (0.47%)  0/99 (0.00%)  1/70 (1.43%) 
Clostridial infection  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Endocarditis  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Lower respiratory tract infection  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Wound infection staphylococcal  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Arthritis bacterial  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Device related infection  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Infected seroma  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Infected skin ulcer  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Pneumonia bacterial  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Respiratory tract infection  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Skin infection  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Streptococcal sepsis  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Urosepsis  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Injury, poisoning and procedural complications       
Infusion related reaction  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Ankle fracture  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Investigations       
Blood bilirubin increased  1  1/211 (0.47%)  1/99 (1.01%)  0/70 (0.00%) 
Ejection fraction decreased  1  2/211 (0.95%)  0/99 (0.00%)  0/70 (0.00%) 
Hemoglobin decreased  1  1/211 (0.47%)  1/99 (1.01%)  0/70 (0.00%) 
Alanine aminotransferase increased  1  2/211 (0.95%)  0/99 (0.00%)  0/70 (0.00%) 
Blood albumin decreased  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Blood creatine phosphokinase increased  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Hepatic enzyme increased  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Aspartate aminotransferase increased  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  1/211 (0.47%)  1/99 (1.01%)  0/70 (0.00%) 
Decreased appetite  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Rhabdomyolysis  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Arthralgia  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Myopathy  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  2  2/211 (0.95%)  0/99 (0.00%)  1/70 (1.43%) 
Rectal cancer  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Prostate cancer  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Nervous system disorders       
Epilepsy  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Ischemic stroke  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Syncope  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Carotid artery dissection  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Headache  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Migraine  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Aphasia  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Psychiatric disorders       
Anxiety  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Hallucination  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Renal and urinary disorders       
Renal failure  1  2/211 (0.95%)  0/99 (0.00%)  0/70 (0.00%) 
Ureterolithiasis  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Urinary retention  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Reproductive system and breast disorders       
Testicular pain  1  0/211 (0.00%)  1/99 (1.01%)  0/70 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1  3/211 (1.42%)  0/99 (0.00%)  1/70 (1.43%) 
Dyspnea  1  3/211 (1.42%)  0/99 (0.00%)  0/70 (0.00%) 
Pleural effusion  1  2/211 (0.95%)  0/99 (0.00%)  0/70 (0.00%) 
Pneumonitis  1  4/211 (1.90%)  0/99 (0.00%)  1/70 (1.43%) 
Interstitial lung disease  1  2/211 (0.95%)  0/99 (0.00%)  0/70 (0.00%) 
Haemoptysis  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Pneumothorax  2  0/211 (0.00%)  0/99 (0.00%)  1/70 (1.43%) 
Skin and subcutaneous tissue disorders       
Rash  1  2/211 (0.95%)  0/99 (0.00%)  0/70 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Orthostatic hypotension  1  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Haematoma  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Hypertensive crisis  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
Lymphoedema  2  1/211 (0.47%)  0/99 (0.00%)  0/70 (0.00%) 
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Trametinib Chemotherapy Cross-over From Chemotherapy to Trametinib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   207/211 (98.10%)   88/99 (88.89%)   66/70 (94.29%) 
Blood and lymphatic system disorders       
Anemia  1  13/211 (6.16%)  10/99 (10.10%)  0/70 (0.00%) 
Neutropenia  1  5/211 (2.37%)  6/99 (6.06%)  0/70 (0.00%) 
Thrombocytopenia  1  2/211 (0.95%)  5/99 (5.05%)  0/70 (0.00%) 
Gastrointestinal disorders       
Diarrhea  1  94/211 (44.55%)  16/99 (16.16%)  24/70 (34.29%) 
Nausea  1  48/211 (22.75%)  39/99 (39.39%)  12/70 (17.14%) 
Constipation  1  34/211 (16.11%)  22/99 (22.22%)  12/70 (17.14%) 
Vomiting  1  33/211 (15.64%)  21/99 (21.21%)  16/70 (22.86%) 
Dry mouth  1  19/211 (9.00%)  2/99 (2.02%)  6/70 (8.57%) 
Abdominal pain  1  19/211 (9.00%)  2/99 (2.02%)  0/70 (0.00%) 
Abdominal pain upper  1  16/211 (7.58%)  3/99 (3.03%)  4/70 (5.71%) 
Stomatitis  1  13/211 (6.16%)  1/99 (1.01%)  0/70 (0.00%) 
General disorders       
Fatigue  1  62/211 (29.38%)  29/99 (29.29%)  8/70 (11.43%) 
Asthenia  1  12/211 (5.69%)  12/99 (12.12%)  4/70 (5.71%) 
Pyrexia  1  15/211 (7.11%)  8/99 (8.08%)  6/70 (8.57%) 
Mucosal inflammation  1  15/211 (7.11%)  0/99 (0.00%)  6/70 (8.57%) 
Oedema peripheral  2  55/211 (26.07%)  2/99 (2.02%)  16/70 (22.86%) 
Inflammation  2  0/211 (0.00%)  0/99 (0.00%)  4/70 (5.71%) 
Influenza like illness  2  0/211 (0.00%)  0/99 (0.00%)  4/70 (5.71%) 
Peripheral swelling  2  0/211 (0.00%)  0/99 (0.00%)  4/70 (5.71%) 
Infections and infestations       
Folliculitis  1  22/211 (10.43%)  2/99 (2.02%)  6/70 (8.57%) 
Paronychia  1  26/211 (12.32%)  1/99 (1.01%)  10/70 (14.29%) 
Nasopharyngitis  2  15/211 (7.11%)  4/99 (4.04%)  0/70 (0.00%) 
Rash pustular  2  11/211 (5.21%)  0/99 (0.00%)  5/70 (7.14%) 
Cellulitis  2  0/211 (0.00%)  0/99 (0.00%)  4/70 (5.71%) 
Nail infection  2  0/211 (0.00%)  0/99 (0.00%)  4/70 (5.71%) 
Investigations       
Aspartate aminotransferase increased  1  21/211 (9.95%)  1/99 (1.01%)  7/70 (10.00%) 
Alanine aminotransferase increased  1  16/211 (7.58%)  3/99 (3.03%)  0/70 (0.00%) 
Blood alkaline phosphatase increased  1  13/211 (6.16%)  1/99 (1.01%)  0/70 (0.00%) 
Neutrophil count decreased  1  2/211 (0.95%)  5/99 (5.05%)  0/70 (0.00%) 
Platelet count decreased  1  1/211 (0.47%)  5/99 (5.05%)  0/70 (0.00%) 
Weight decreased  2  0/211 (0.00%)  0/99 (0.00%)  4/70 (5.71%) 
Metabolism and nutrition disorders       
Decreased appetite  1  18/211 (8.53%)  10/99 (10.10%)  6/70 (8.57%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  19/211 (9.00%)  10/99 (10.10%)  0/70 (0.00%) 
Back pain  1  18/211 (8.53%)  9/99 (9.09%)  0/70 (0.00%) 
Pain in extremity  1  13/211 (6.16%)  8/99 (8.08%)  4/70 (5.71%) 
Myalgia  1  3/211 (1.42%)  6/99 (6.06%)  0/70 (0.00%) 
Nervous system disorders       
Headache  1  30/211 (14.22%)  15/99 (15.15%)  0/70 (0.00%) 
Paraesthesia  1  10/211 (4.74%)  9/99 (9.09%)  0/70 (0.00%) 
Peripheral sensory neuropathy  1  3/211 (1.42%)  9/99 (9.09%)  0/70 (0.00%) 
Dysgeusia  2  12/211 (5.69%)  1/99 (1.01%)  0/70 (0.00%) 
Dizziness  2  0/211 (0.00%)  0/99 (0.00%)  7/70 (10.00%) 
Psychiatric disorders       
Insomnia  1  15/211 (7.11%)  7/99 (7.07%)  4/70 (5.71%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  24/211 (11.37%)  6/99 (6.06%)  4/70 (5.71%) 
Dyspnea  1  15/211 (7.11%)  6/99 (6.06%)  4/70 (5.71%) 
Epistaxis  1  15/211 (7.11%)  1/99 (1.01%)  4/70 (5.71%) 
Skin and subcutaneous tissue disorders       
Rash  1  123/211 (58.29%)  10/99 (10.10%)  37/70 (52.86%) 
Alopecia  1  38/211 (18.01%)  19/99 (19.19%)  7/70 (10.00%) 
Dermatitis acneiform  1  42/211 (19.91%)  2/99 (2.02%)  10/70 (14.29%) 
Dry skin  1  30/211 (14.22%)  1/99 (1.01%)  10/70 (14.29%) 
Pruritus  1  25/211 (11.85%)  1/99 (1.01%)  10/70 (14.29%) 
Eczema  1  12/211 (5.69%)  0/99 (0.00%)  6/70 (8.57%) 
Hyperhidrosis  2  0/211 (0.00%)  6/99 (6.06%)  0/70 (0.00%) 
Skin fissures  2  21/211 (9.95%)  0/99 (0.00%)  9/70 (12.86%) 
Rash macular  2  0/211 (0.00%)  0/99 (0.00%)  5/70 (7.14%) 
Rash maculo-papular  2  0/211 (0.00%)  0/99 (0.00%)  4/70 (5.71%) 
Vascular disorders       
Hypertension  1  40/211 (18.96%)  9/99 (9.09%)  9/70 (12.86%) 
Lymphedema  1  18/211 (8.53%)  0/99 (0.00%)  6/70 (8.57%) 
1
Term from vocabulary, MedDRA
2
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
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
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01245062     History of Changes
Other Study ID Numbers: 114267
First Submitted: November 18, 2010
First Posted: November 22, 2010
Results First Submitted: February 14, 2013
Results First Posted: March 15, 2013
Last Update Posted: April 5, 2018