Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 13 of 510 for:    melanoma phase III

A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

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: NCT01584648
Recruitment Status : Completed
First Posted : April 25, 2012
Results First Posted : August 15, 2014
Last Update Posted : April 25, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Melanoma
Interventions Drug: dabrafenib
Drug: dabrafenib plus trametinib placebo
Drug: Trametinib
Enrollment 422
Recruitment Details Participants (par.) with advanced or metastatic (Stage IIIc or Stage IV) BRAF V600E/K mutation-positive melanoma were enrolled in this randomized, double-blinded, multi-center Phase III study.
Pre-assignment Details  
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Period Title: Overall Study
Started 211 212
Ongoing 154 147
Completed 0 0
Not Completed 211 212
Reason Not Completed
Lost to Follow-up             4             3
Physician Decision             2             2
Withdrawal by Subject             11             5
Death             40             55
Ongoing             154             147
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo Total
Hide Arm/Group Description Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Total of all reporting groups
Overall Number of Baseline Participants 211 212 423
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 211 participants 212 participants 423 participants
55.1  (13.33) 55.3  (13.75) 55.2  (13.52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 211 participants 212 participants 423 participants
Female
100
  47.4%
98
  46.2%
198
  46.8%
Male
111
  52.6%
114
  53.8%
225
  53.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 211 participants 212 participants 423 participants
African American/African Heritage
0
   0.0%
1
   0.5%
1
   0.2%
White - White/Caucasian/European Heritage
211
 100.0%
211
  99.5%
422
  99.8%
1.Primary Outcome
Title Progression-Free Survival (PFS) as Assessed by the Investigator
Hide Description Progression-free survival (PFS) is defined as the time (in months) from the date of randomization to the first documented occurrence of PD or death. Investigator PFS was summarized per response evaluation criteria in solid tumors (RECIST, version 1.1) which is a set of published criteria defining when cancer patients improve (respond), stay the same (stable) or worsen (progress). 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 5mm or the appearance of one or more new lesions, or the worsening of non target lesions significant enough to require study treatment discontinuation. For participants who had not progressed or died at the time of the analysis, censoring was performed at the last adequate disease assessment.
Time Frame From randomization until the earliest date of disease progression (PD) or death due to any cause (average of 9 study months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants regardless of whether or not they received the study treatment. Any participant who received a treatment randomization number was considered to have been randomized.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 211 212
Median (95% Confidence Interval)
Unit of Measure: Months
9.3
(7.7 to 11.1)
8.8
(5.9 to 10.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabrafenib + Trametinib, Dabrafenib + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Log Rank
Comments p-value from stratified log-rank test was adjusted for randomized strata: Baseline lactate dehydrogenase (LDH) and BRAF mutation status
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.57 to 0.99
Estimation Comments Hazard ratios (HRs) were estimated using a Pike estimator. HRs were adjusted for randomized strata: Baseline LDH and BRAF mutation status.
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the interval of time (in months) between the date of randomization and the date of death due to any cause. For participants who did not die, time of death was censored at the date of last contact.
Time Frame From randomization until death due to any cause (average of 9 study months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 211 212
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(14.1 to NA)
NA [2] 
(NA to NA)
[1]
There were too few events to provide an estimable median or upper limit of the 95 % CI.
[2]
There were too few events to provide an estimable median, lower limit and upper limit of the 95% CI.
3.Secondary Outcome
Title Number of Participants With a Confirmed Response (Complete Response or Partial Response)
Hide Description A participant was defined as a responder if he/she sustained a complete response (CR: the disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions) or partial response (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 or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm).
Time Frame From randomization until the first documented complete response or partial response (average of 9 study months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with measurable disease at Baseline per RECIST were analyzed.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 210 210
Measure Type: Number
Unit of Measure: Participants
140 108
4.Secondary Outcome
Title Duration of Response for Participants With a Confirmed Response (Complete Response or Partial Response)
Hide Description Duration of response is defined as the time (in months) from the first documented complete response (CR: the disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions) or partial response (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 or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm) until disease progression (PD). 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 5mm or the appearance of one or more new lesions, or the worsening of non target lesions significant enough to require study treatment discontinuation. PD was based on the radiological evidence by investigator.
Time Frame From the time of the first documented response (CR or PR) until disease progression (average of 9 study months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants with a confirmed CR or PR were analyzed (with or without measurabe disease at Baseline).
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 140 109
Median (95% Confidence Interval)
Unit of Measure: Months
9.2 [1] 
(7.4 to NA)
10.2 [1] 
(7.5 to NA)
[1]
There were too few events to provide an estimable upper limit of the 95 % CI.
5.Secondary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Hide Description An AE is defined as any untoward medical occurrence in a par., temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as 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, or is a congenital anomaly/birth defect. Protocol specific SAEs included: ALT≥3XULN and total bilirubin ≥2XULN (35% direct) or ALT ≥3XULN and INR >1.5 (if INR is measured); any new malignancy with a histology different from the primary tumor; left ventricular ejection fraction that met stopping criteria; central serous retinopathy or retinal vein occlusion; pyrexia accompanied by ≥grade 3 hypotension, or hypotension that is clinically significant as judged by the investigator, dehydration requiring IV fluids, or severe rigor/chills. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time Frame From the time the first dose of study treatment administered until 30 days after discontinuation of study treatment (average of 9 study months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all randomized participants who received at least one dose of study medication and were based on the actual treatment received if this differed from that to which the participant was randomized.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 209 211
Measure Type: Number
Unit of Measure: Participants
Any AEs 199 203
Any SAEs 73 64
6.Secondary Outcome
Title Number of Participants With a Worst-case On-therapy Grade Change From Baseline to Grade 3 and 4 for the Indicated Clinical Chemistry Parameters
Hide Description Clinical chemistry data were summarized according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe or disabling; Grade 4, Life-threatening; Grade 5, Death related to AE. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Clinical chemistry tests where the toxicity grade is defined by NCI-CTCAE includes albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, calcium, glucose, potassium, sodium, creatinine and phosphate. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. Only those participants with laboratory values for worst-case on-therapy are presented. Worst-case on-therapy included both scheduled and unscheduled visits.
Time Frame From Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 209 211
Measure Type: Number
Unit of Measure: Participants
Albumin (Low), Grade 3 Number Analyzed 208 participants 209 participants
3 0
Albumin (Low), Grade 4 Number Analyzed 208 participants 209 participants
0 0
Alkaline Phosphatase, Grade 3 Number Analyzed 208 participants 209 participants
2 1
Alkaline Phosphatase, Grade 4 Number Analyzed 208 participants 209 participants
0 0
ALT Grade 3 Number Analyzed 208 participants 209 participants
7 2
ALT, Grade 4 Number Analyzed 208 participants 209 participants
1 0
AST, Grade 3 Number Analyzed 208 participants 208 participants
7 2
AST, Grade 4 Number Analyzed 208 participants 208 participants
1 0
Bilirubin, Grade 3 Number Analyzed 207 participants 209 participants
2 0
Bilirubin, Grade 4 Number Analyzed 207 participants 209 participants
1 0
Creatinine, Grade 3 Number Analyzed 208 participants 209 participants
1 1
Creatinine, Grade 4 Number Analyzed 208 participants 209 participants
0 0
Phosphate, Grade 3 Number Analyzed 208 participants 208 participants
7 12
Phosphate, Grade 4 Number Analyzed 208 participants 208 participants
0 1
Calcium (hypercalcemia), Grade 3 Number Analyzed 208 participants 209 participants
0 2
Calcium (hypercalcemia), Grade 4 Number Analyzed 208 participants 209 participants
0 0
Calcium (hypocalcemia), Grade 3 Number Analyzed 208 participants 209 participants
0 0
Calcium (hypocalcemia), Grade 4 Number Analyzed 208 participants 209 participants
0 0
Glucose (hyperglycemia), Grade 3 Number Analyzed 208 participants 209 participants
10 7
Glucose (hyperglycemia), Grade 4 Number Analyzed 208 participants 209 participants
0 0
Glucose (hypoglycemia), Grade 3 Number Analyzed 208 participants 209 participants
1 0
Glucose (hypoglycemia), Grade 4 Number Analyzed 208 participants 209 participants
0 0
Potassium (hyperkalemia), Grade 3 Number Analyzed 208 participants 209 participants
3 2
Potassium (hyperkalemia), Grade 4 Number Analyzed 208 participants 209 participants
0 0
Potassium (hypokalemia), Grade 3 Number Analyzed 208 participants 209 participants
4 4
Potassium (hypokalemia), Grade 4 Number Analyzed 208 participants 209 participants
0 1
Sodium (hypernatremia), Grade 3 Number Analyzed 208 participants 209 participants
0 0
Sodium (hypernatremia), Grade 4 Number Analyzed 208 participants 209 participants
0 0
Sodium (hyponatremia), Grade 3 Number Analyzed 208 participants 209 participants
10 5
Sodium (hyponatremia), Grade 4 Number Analyzed 208 participants 209 participants
0 0
7.Secondary Outcome
Title Number of Participants With a Worst-case On-therapy Grade Change From Baseline to Grade 3 and 4 for the Indicated Hematology Parameters
Hide Description Hematology data were summarized according to NCI-CTCAE grade, version 4.0. Grade 1, Mild; Grade 2, Moderate; Grade 3, Severe, or disabling; Grade 4, Life-threatening; Grade 5, Death related to AE. Data are presented for only those parameters for which an increase to Grade 3 or Grade 4 occurred. Hematology tests where the toxicity grade is defined by NCI-CTCAE includes hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Participants with missing Baseline grades were assumed to have a Baseline grade of 0. Only those participants with laboratory values for worst-case on-therapy are presented. Worst-case on-therapy included both scheduled and unscheduled visits.
Time Frame From Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 208 208
Measure Type: Number
Unit of Measure: Participants
Anaemia, Grade 3 3 7
Anaemia, Grade 4 0 0
Hemoglobin (Increased), Grade 3 1 0
Hemoglobin (Increased), Grade 4 0 0
Lymphocytes (Decreased), Grade 3 14 15
Lymphocytes (Decreased), Grade 4 3 0
Lymphocytes (Increased), Grade 3 0 0
Lymphocytes (Increased), Grade 4 0 0
Neutrophils, Grade 3 12 2
Neutrophils, Grade 0 1
Platelets, Grade 3 1 0
Platelets, Grade 4 0 1
Leukocytes, Grade 3 4 1
Leukocytes, Grade 4 0 0
8.Secondary Outcome
Title Number of Participants With a Worst-case On-therapy Change From Baseline With Respect to the Normal Range for the Indicated Hematology Parameters
Hide Description Hematology tests where the toxicity grade is not defined by NCI-CTCAE includes basophils, eosinophils and monocytes. Change from Baseline is categorized as a decrease to low, change to normal or no change, increase to high in reference to the normal range. Only those participants with laboratory values for worst-case on-therapy are presented. For the worst-case on-therapy, participants were counted twice if the participant lab value decreased to low and increased to high during the on-therapy period.
Time Frame From Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 208 208
Measure Type: Number
Unit of Measure: Participants
Basophils, Decrease to Low 6 6
Basophils, No Change 199 196
Basophils, Increase to High 3 6
Eosinophils, Decrease to Low 13 7
Eosinophils, No Change 187 192
Eosinophils, Increase to High, n=208, 208 8 9
Monocytes, Decrease to Low 18 5
Monocytes, No Change 178 179
Monocytes, Increase to High 15 24
9.Secondary Outcome
Title Number of Participants With a Worst-case On-therapy Change From Baseline With Respect to the Normal Range for the Indicated Clinical Chemistry Parameters
Hide Description Clinical chemistry tests where the toxicity grade is not defined by NCI-CTCAE includes chloride, creatinine clearence, lactate dehydrogenase, urea, protein and carbon dioxide. Change from Baseline is categorized as decrease to low, change to normal or no change, increase to high in reference to the normal range. Only those participants with laboratory values for worst-case on-therapy are presented. For the worst-case on-therapy, participants were counted twice if the participant lab value decreased to low and increased to high during the on-therapy period.
Time Frame From Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the Safety Population.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 209 211
Measure Type: Number
Unit of Measure: Participants
Chloride, Decrease to Low Number Analyzed 208 participants 208 participants
19 12
Chloride, No Change, n=208, 208 Number Analyzed 208 participants 208 participants
184 191
Chloride, Increase to High Number Analyzed 208 participants 208 participants
5 5
Lactate dehydrogenase, Decrease to Low Number Analyzed 207 participants 208 participants
1 4
Lactate dehydrogenase, No Change Number Analyzed 207 participants 208 participants
117 181
Lactate dehydrogenase,Increase to High Number Analyzed 207 participants 208 participants
89 25
Urea, Decrease to Low Number Analyzed 208 participants 209 participants
11 3
Urea, No Change Number Analyzed 208 participants 209 participants
162 181
Urea, Increase to High Number Analyzed 208 participants 209 participants
35 26
Creatinine clearance, Decrease to Low Number Analyzed 16 participants 10 participants
9 3
Creatinine clearance, No Change Number Analyzed 16 participants 10 participants
7 5
Creatinine clearance, Increase to High Number Analyzed 16 participants 10 participants
0 2
Protein, Decrease to Low Number Analyzed 208 participants 208 participants
29 26
Protein, No Change Number Analyzed 209 participants 211 participants
208 208
Protein, Increase to High Number Analyzed 208 participants 208 participants
5 6
Carbon Dioxide, Decrease to Low Number Analyzed 208 participants 208 participants
15 16
Carbon Dioxide, No Change Number Analyzed 208 participants 208 participants
186 192
Carbon Dioxide, Increase to High Number Analyzed 208 participants 208 participants
9 1
10.Secondary Outcome
Title Number of Participants With a Worst-case On-therapy Change From Baseline in Heart Rate
Hide Description Change from Baseline in heart rate is categorized as decrease to <60 beats per minute (bpm), change to normal or no change, and increase to >100 bpm. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant heart rate value decreased to <60 bpm and increased to >100 bpm post-Baseline. Only those participants with heart rate values for worst-case on-therapy are presented.
Time Frame From Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 208 208
Measure Type: Number
Unit of Measure: Participants
Decrease to <60 36 19
No Change 145 157
Increase to >100 30 34
11.Secondary Outcome
Title Number of Participants With a Worst-case On-therapy Change From Baseline in Systolic and Diastolic Blood Pressure to Grade 2 or Grade 3
Hide Description Change from Baseline in systolic blood pressure (SBP) is categorized as: Grade 0 (<120 millimeters of mercury [mmHg]), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), and Grade 3 (>=160 mmHg). Change from Baseline in diastolic blood pressure (DBP) is categorized as: Grade 0 (<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), and Grade 3 (>=100 mmHg). An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Participants with missing Baseline values were assumed to have a Baseline value of grade 0. Only those participants with blood pressure values for worst-case on-therapy are presented.
Time Frame From Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 208 208
Measure Type: Number
Unit of Measure: Participants
DBP, Increase to Grade 2 55 26
DBP, Increase to Grade 3 16 7
SBP, Increase to Grade 2 47 42
SBP, Increase to Grade 3 22 14
12.Secondary Outcome
Title Number of Participants With a Worst-case On-therapy Change From Baseline in Temperature
Hide Description Change from Baseline in temperature is categorized as a decrease to <=35 degrees celsius (C), change to normal or no change as 35-38 degrees C, and increase to >=38 degrees C. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant temperature value decreased to <=35 degrees C and increased to >=38 degrees C post-Baseline. Only those participants with temperature values for worst-case on-therapy are presented.
Time Frame From Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 208 208
Measure Type: Number
Unit of Measure: Participants
Decrease to <=35 5 7
No Change 166 185
Increase to >=38 38 16
13.Secondary Outcome
Title Number of Participants With a Worse-case On-therapy Change From Baseline in the Bazett's QTc to Grade 2 or Grade 3
Hide Description The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. Bazett's QTc is categorized as: Grade 0 (<450 milliseconds [msec]), Grade 1 (450-480 msec), Grade 2 (481-500 msec), and Grade 3 (>=501 msec). An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Participants with missing Baseline values were assumed to have a Baseline value of grade 0. Only those participants with Bazett's QTc values for worst-case on-therapy are presented.
Time Frame From Baseline up to Week 60
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 195 192
Measure Type: Number
Unit of Measure: Participants
Increase to Grade 2 4 6
Increase to Grade 3 0 2
14.Secondary Outcome
Title Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram
Hide Description Absolute change from Baseline in LVEF were summarized at each scheduled assessment time and in the worst-case post Baseline. Only the post Baseline assessments that used the same method (ECHO or Multi Gated Acquisition Scan [MUGA]) as the Baseline assessments were used to derive the change from Baseline. The change from Baseline was categorized as any increase; no change; and any decrease and as 0-10 decrease, 10 - 19 decrease, >= 20 decrease, >=10 decrease and >= lower limit of normal (LLN), >=10 decrease and <LLN, >10 decrease and <LLN, >= 20 decrease and >= LLN, >= 20 decrease and <LLN. Only those participants with LVEF values for worst-case on-therapy are presented.
Time Frame From Baseline up to Week 60
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 206 207
Measure Type: Number
Unit of Measure: Participants
No Change 30 36
Any Increase 34 55
Any Decrease 142 116
0-<10 decrease 105 91
10 - 19 decrease 33 21
>= 20 decrease 4 4
>=10 decrease and >=LLN 29 20
>=10 decrease and <LLN 8 5
>10 decrease and <LLN 6 5
>= 20 decrease and >= LLN 2 1
>= 20 decrease and <LLN 2 3
15.Secondary Outcome
Title Number of Participants With Incidence of Squamous Cell Carcinoma
Hide Description Participants were evaluated for the event of squamous cell carcinoma including Keratoacanthoma.
Time Frame From Baseline up to end of study (average of 9 study months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 209 211
Measure Type: Number
Unit of Measure: participants
5 20
16.Secondary Outcome
Title Plasma Concentrations of Trametinib
Hide Description Blood samples were collected for Pharmacokinetic (PK) analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24.
Time Frame Week 8: pre-dose, 1-3 hours and 4-6 hours post dose; Week 16 pre-dose and Week 24 pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) Population: all participants included in the safety population for whom a PK sample was obtained and analyzed. Only participants with data available at the specified time points were analyzed.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 203 194
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
Week 8, pre-dose Number Analyzed 176 participants 170 participants
9.209  (3.86587) 0.000  (0.000)
Week 8, 1-3 hours Number Analyzed 176 participants 176 participants
19.0382  (6.86542) 0.0261  (0.34598)
Week 8, 4-6 hours Number Analyzed 174 participants 171 participants
16.7496  (5.64363) 0.000  (0.000)
Week 16 pre-dose Number Analyzed 179 participants 162 participants
11.0385  (4.79185) 0.0039  (0.03548)
Week 24 pre-dose Number Analyzed 157 participants 130 participants
11.5167  (5.19171) 0.0548  (0.62447)
17.Secondary Outcome
Title Plasma Concentrations of Dabrafenib and Its Metabolites
Hide Description Blood samples were collected for PK analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Plasma concentrations of dabrafenib (GSK2118436) and its metabolites (GSK2285403, GSK2298683, and GSK2167542) were determined using the currently approved analytical methodology.
Time Frame Week 8: pre-dose, 1-3 hours and 4-6 hours post dose; Week 16 pre-dose and Week 24 pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population.
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description:
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
Overall Number of Participants Analyzed 203 194
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
GSK2118436, Week 8, pre-dose Number Analyzed 176 participants 170 participants
92.1  (204.85) 64.4  (96.98)
GSK2118436, Week 8, 1-3 hours Number Analyzed 176 participants 176 participants
1309.6  (982.25) 1362.3  (992.97)
GSK2118436, Week 8, 4-6 hours Number Analyzed 173 participants 171 participants
458.9  (318.59) 539.7  (553.09)
GSK2118436, Week 16 pre-dose Number Analyzed 179 participants 162 participants
151.6  (261.31) 151.2  (381.32)
GSK2118436, Week 24 pre-dose Number Analyzed 157 participants 130 participants
167.0  (346.97) 156.5  (357.50)
GSK2285403, Week 8, pre-dose Number Analyzed 176 participants 170 participants
82.0  (123.93) 76.7  (109.09)
GSK2285403, Week 8, 1-3 hours Number Analyzed 176 participants 176 participants
648.5  (459.01) 672.7  (519.45)
GSK2285403, Week 8, 4-6 hours Number Analyzed 174 participants 171 participants
391.3  (206.70) 502.2  (356.72)
GSK2285403, Week 16 pre-dose Number Analyzed 179 participants 162 participants
128.7  (174.26) 121.1  (195.15)
GSK2285403, Week 24 pre-dose Number Analyzed 157 participants 130 participants
126.1  (219.82) 145.7  (265.57)
GSK2298683, Week 8, pre-dose Number Analyzed 176 participants 172 participants
3237.2  (1694.66) 3469.4  (1854.02)
GSK2298683,Week 8, 1-3 hours Number Analyzed 177 participants 179 participants
4286.3  (2514.50) 4456.6  (2687.32)
GSK2298683, Week 8, 4-6 hours Number Analyzed 174 participants 173 participants
6238.3  (2716.05) 6891.6  (2739.07)
GSK2298683, Week 16 pre-dose Number Analyzed 179 participants 163 participants
3842.4  (2428.74) 4114.1  (2432.72)
GSK2298683,Week 24 pre-dose Number Analyzed 156 participants 130 participants
3617.9  (2645.51) 4193.2  (2730.78)
GSK2167542, Week 8, pre-dose Number Analyzed 176 participants 170 participants
346.6  (261.73) 308.9  (224.56)
GSK2167542, Week 8, 1-3 hours Number Analyzed 176 participants 176 participants
361.7  (245.92) 341.8  (240.96)
GSK2167542, Week 8, 4-6 hours Number Analyzed 174 participants 171 participants
316.9  (208.51) 328.1  (234.95)
GSK2167542, Week 16 pre-dose Number Analyzed 179 participants 162 participants
335.0  (228.26) 331.0  (250.04)
GSK2167542, Week 24 pre-dose Number Analyzed 157 participants 130 participants
306.2  (203.77) 312.8  (250.28)
Time Frame On-treatment serious adverse events (SAEs) and non-serious AE are presented from the time the first dose of study treatment was administered until 30 days after discontinuation of study treatment (average of 9 study months)
Adverse Event Reporting Description SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all randomized participants who received at least one dose of study medication and were based on the actual treatment received.
 
Arm/Group Title Dabrafenib + Trametinib Dabrafenib + Placebo
Hide Arm/Group Description Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
All-Cause Mortality
Dabrafenib + Trametinib Dabrafenib + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Dabrafenib + Trametinib Dabrafenib + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   73/209 (34.93%)   64/211 (30.33%) 
Blood and lymphatic system disorders     
Anaemia  1  2/209 (0.96%)  3/211 (1.42%) 
Haemolytic uraemic syndrome  1  1/209 (0.48%)  0/211 (0.00%) 
Neutropenia  1  1/209 (0.48%)  0/211 (0.00%) 
Pancytopenia  1  1/209 (0.48%)  0/211 (0.00%) 
Thrombocytopenia  1  1/209 (0.48%)  0/211 (0.00%) 
Febrile neutropenia  1  0/209 (0.00%)  2/211 (0.95%) 
Cardiac disorders     
Atrial fibrillation  1  2/209 (0.96%)  2/211 (0.95%) 
Supraventricular tachycardia  1  1/209 (0.48%)  0/211 (0.00%) 
Cardiac failure  1  0/209 (0.00%)  1/211 (0.47%) 
Tachycardia  1  0/209 (0.00%)  1/211 (0.47%) 
Eye disorders     
Chorioretinopathy  1  1/209 (0.48%)  1/211 (0.47%) 
Iridocyclitis  1  1/209 (0.48%)  0/211 (0.00%) 
Retinal detachment  1  1/209 (0.48%)  0/211 (0.00%) 
Uveitis  1  0/209 (0.00%)  1/211 (0.47%) 
Visual impairment  1  0/209 (0.00%)  1/211 (0.47%) 
Gastrointestinal disorders     
Abdominal pain  1  3/209 (1.44%)  1/211 (0.47%) 
Vomiting  1  3/209 (1.44%)  0/211 (0.00%) 
Nausea  1  2/209 (0.96%)  0/211 (0.00%) 
Abdominal pain upper  1  1/209 (0.48%)  0/211 (0.00%) 
Constipation  1  1/209 (0.48%)  0/211 (0.00%) 
Diarrhoea  1  1/209 (0.48%)  0/211 (0.00%) 
Rectal haemorrhage  1  1/209 (0.48%)  0/211 (0.00%) 
Colitis  1  0/209 (0.00%)  1/211 (0.47%) 
Peritoneal haemorrhage  1  0/209 (0.00%)  1/211 (0.47%) 
Upper gastrointestinal haemorrhage  1  0/209 (0.00%)  1/211 (0.47%) 
General disorders     
Pyrexia  1  31/209 (14.83%)  14/211 (6.64%) 
Chills  1  8/209 (3.83%)  2/211 (0.95%) 
Fatigue  1  3/209 (1.44%)  1/211 (0.47%) 
General physical health deterioration  1  1/209 (0.48%)  0/211 (0.00%) 
Influenza like illness  1  1/209 (0.48%)  0/211 (0.00%) 
Axillary pain  1  0/209 (0.00%)  1/211 (0.47%) 
Chest pain  1  0/209 (0.00%)  1/211 (0.47%) 
Malaise  1  0/209 (0.00%)  1/211 (0.47%) 
Oedema peripheral  1  0/209 (0.00%)  1/211 (0.47%) 
Infections and infestations     
Pneumonia  1  3/209 (1.44%)  2/211 (0.95%) 
Bacteraemia  1  1/209 (0.48%)  0/211 (0.00%) 
Cellulitis  1  1/209 (0.48%)  1/211 (0.47%) 
Kidney infection  1  1/209 (0.48%)  0/211 (0.00%) 
Neutropenic sepsis  1  1/209 (0.48%)  0/211 (0.00%) 
Pyelonephritis  1  1/209 (0.48%)  0/211 (0.00%) 
Sepsis  1  1/209 (0.48%)  1/211 (0.47%) 
Staphylococcal sepsis  1  1/209 (0.48%)  0/211 (0.00%) 
Superinfection  1  1/209 (0.48%)  0/211 (0.00%) 
Urosepsis  1  1/209 (0.48%)  0/211 (0.00%) 
Peritonitis  1  0/209 (0.00%)  1/211 (0.47%) 
Urinary tract infection  1  0/209 (0.00%)  1/211 (0.47%) 
Injury, poisoning and procedural complications     
Hepatic haematoma  1  1/209 (0.48%)  0/211 (0.00%) 
Investigations     
Ejection fraction decreased  1  6/209 (2.87%)  5/211 (2.37%) 
Alanine aminotransferase increased  1  3/209 (1.44%)  1/211 (0.47%) 
Aspartate aminotransferase increased  1  1/209 (0.48%)  0/211 (0.00%) 
Blood alkaline phosphatase increased  1  1/209 (0.48%)  0/211 (0.00%) 
Haemoglobin decreased  1  1/209 (0.48%)  0/211 (0.00%) 
Hepatic enzyme increased  1  1/209 (0.48%)  0/211 (0.00%) 
Neutrophil count decreased  1  1/209 (0.48%)  0/211 (0.00%) 
Transaminases increased  1  1/209 (0.48%)  0/211 (0.00%) 
White blood cell count decreased  1  1/209 (0.48%)  0/211 (0.00%) 
Venous pressure jugular increased  1  0/209 (0.00%)  1/211 (0.47%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  2/209 (0.96%)  0/211 (0.00%) 
Dehydration  1  1/209 (0.48%)  2/211 (0.95%) 
Hypokalaemia  1  1/209 (0.48%)  0/211 (0.00%) 
Hypophosphataemia  1  1/209 (0.48%)  0/211 (0.00%) 
Hypercalcaemia  1  0/209 (0.00%)  1/211 (0.47%) 
Hyponatraemia  1  0/209 (0.00%)  1/211 (0.47%) 
Type 2 diabetes mellitus  1  0/209 (0.00%)  1/211 (0.47%) 
Musculoskeletal and connective tissue disorders     
Hypercreatinaemia  1  1/209 (0.48%)  0/211 (0.00%) 
Intervertebral disc degeneration  1  1/209 (0.48%)  1/211 (0.47%) 
Muscle haemorrhage  1  1/209 (0.48%)  0/211 (0.00%) 
Back pain  1  0/209 (0.00%)  1/211 (0.47%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  4/209 (1.91%)  8/211 (3.79%) 
Squamous cell carcinoma  1  2/209 (0.96%)  8/211 (3.79%) 
Squamous cell carcinoma of skin  1  2/209 (0.96%)  10/211 (4.74%) 
Malignant melanoma  1  1/209 (0.48%)  2/211 (0.95%) 
Metastases to central nervous system  1  1/209 (0.48%)  0/211 (0.00%) 
Papillary thyroid cancer  1  1/209 (0.48%)  0/211 (0.00%) 
Prostate cancer  1  1/209 (0.48%)  0/211 (0.00%) 
Adenocarcinoma gastric  1  0/209 (0.00%)  1/211 (0.47%) 
Bile duct adenocarcinoma  1  0/209 (0.00%)  1/211 (0.47%) 
Invasive ductal breast carcinoma  1  0/209 (0.00%)  1/211 (0.47%) 
Keratoacanthoma  1  0/209 (0.00%)  1/211 (0.47%) 
Lipofibroma  1  0/209 (0.00%)  1/211 (0.47%) 
Tumour haemorrhage  1  0/209 (0.00%)  1/211 (0.47%) 
Nervous system disorders     
Syncope  1  3/209 (1.44%)  1/211 (0.47%) 
Cerebral haemorrhage  1  2/209 (0.96%)  0/211 (0.00%) 
Cerebrovascular accident  1  1/209 (0.48%)  0/211 (0.00%) 
Dizziness  1  1/209 (0.48%)  0/211 (0.00%) 
Epilepsy  1  1/209 (0.48%)  0/211 (0.00%) 
Sciatica  1  1/209 (0.48%)  0/211 (0.00%) 
Tremor  1  1/209 (0.48%)  0/211 (0.00%) 
VIIth nerve paralysis  1  1/209 (0.48%)  0/211 (0.00%) 
Brain oedema  1  0/209 (0.00%)  1/211 (0.47%) 
Convulsion  1  0/209 (0.00%)  1/211 (0.47%) 
Subarachnoid haemorrhage  1  0/209 (0.00%)  1/211 (0.47%) 
Psychiatric disorders     
Confusional state  1  3/209 (1.44%)  0/211 (0.00%) 
Delirium  1  1/209 (0.48%)  0/211 (0.00%) 
Renal and urinary disorders     
Azotaemia  1  1/209 (0.48%)  0/211 (0.00%) 
Nephritis  1  1/209 (0.48%)  0/211 (0.00%) 
Pelvi-ureteric obstruction  1  1/209 (0.48%)  0/211 (0.00%) 
Urinary retention  1  1/209 (0.48%)  0/211 (0.00%) 
Hydronephrosis  1  0/209 (0.00%)  1/211 (0.47%) 
Renal failure acute  1  0/209 (0.00%)  1/211 (0.47%) 
Respiratory, thoracic and mediastinal disorders     
Nasal polyps  1  1/209 (0.48%)  0/211 (0.00%) 
Pleural effusion  1  1/209 (0.48%)  0/211 (0.00%) 
Pneumonitis  1  1/209 (0.48%)  0/211 (0.00%) 
Pulmonary embolism  1  1/209 (0.48%)  1/211 (0.47%) 
Chronic obstructive pulmonary disease  1  0/209 (0.00%)  1/211 (0.47%) 
Dyspnoea  1  0/209 (0.00%)  2/211 (0.95%) 
Respiratory depression  1  0/209 (0.00%)  1/211 (0.47%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  1/209 (0.48%)  0/211 (0.00%) 
Hyperkeratosis  1  0/209 (0.00%)  1/211 (0.47%) 
Skin lesion  1  0/209 (0.00%)  1/211 (0.47%) 
Skin ulcer  1  0/209 (0.00%)  1/211 (0.47%) 
Vascular disorders     
Hypotension  1  6/209 (2.87%)  2/211 (0.95%) 
Deep vein thrombosis  1  1/209 (0.48%)  0/211 (0.00%) 
Hypertension  1  1/209 (0.48%)  0/211 (0.00%) 
Hypovolaemic shock  1  0/209 (0.00%)  1/211 (0.47%) 
Thrombophlebitis superficial  1  0/209 (0.00%)  1/211 (0.47%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dabrafenib + Trametinib Dabrafenib + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   199/209 (95.22%)   202/211 (95.73%) 
Blood and lymphatic system disorders     
Neutropenia  1  17/209 (8.13%)  2/211 (0.95%) 
Anaemia  1  12/209 (5.74%)  14/211 (6.64%) 
Cardiac disorders     
Tachycardia  1  2/209 (0.96%)  11/211 (5.21%) 
Gastrointestinal disorders     
Nausea  1  63/209 (30.14%)  54/211 (25.59%) 
Diarrhoea  1  50/209 (23.92%)  30/211 (14.22%) 
Vomiting  1  41/209 (19.62%)  29/211 (13.74%) 
Constipation  1  22/209 (10.53%)  18/211 (8.53%) 
Abdominal pain  1  19/209 (9.09%)  13/211 (6.16%) 
Dry mouth  1  16/209 (7.66%)  6/211 (2.84%) 
Abdominal pain upper  1  15/209 (7.18%)  10/211 (4.74%) 
General disorders     
Pyrexia  1  101/209 (48.33%)  52/211 (24.64%) 
Fatigue  1  72/209 (34.45%)  74/211 (35.07%) 
Chills  1  57/209 (27.27%)  32/211 (15.17%) 
Oedema peripheral  1  30/209 (14.35%)  9/211 (4.27%) 
Asthenia  1  20/209 (9.57%)  27/211 (12.80%) 
Influenza like illness  1  14/209 (6.70%)  5/211 (2.37%) 
Infections and infestations     
Nasopharyngitis  1  20/209 (9.57%)  15/211 (7.11%) 
Urinary tract infection  1  15/209 (7.18%)  4/211 (1.90%) 
Investigations     
Aspartate aminotransferase increased  1  22/209 (10.53%)  7/211 (3.32%) 
Alanine aminotransferase increased  1  19/209 (9.09%)  9/211 (4.27%) 
Blood alkaline phosphatase increased  1  12/209 (5.74%)  6/211 (2.84%) 
Weight decreased  1  10/209 (4.78%)  14/211 (6.64%) 
Metabolism and nutrition disorders     
Decreased appetite  1  23/209 (11.00%)  25/211 (11.85%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  51/209 (24.40%)  58/211 (27.49%) 
Pain in extremity  1  30/209 (14.35%)  33/211 (15.64%) 
Myalgia  1  22/209 (10.53%)  24/211 (11.37%) 
Back pain  1  19/209 (9.09%)  29/211 (13.74%) 
Muscle spasms  1  16/209 (7.66%)  6/211 (2.84%) 
Musculoskeletal pain  1  2/209 (0.96%)  12/211 (5.69%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Seborrhoeic keratosis  1  7/209 (3.35%)  18/211 (8.53%) 
Skin papilloma  1  3/209 (1.44%)  45/211 (21.33%) 
Melanocytic naevus  1  2/209 (0.96%)  15/211 (7.11%) 
Nervous system disorders     
Headache  1  63/209 (30.14%)  62/211 (29.38%) 
Dizziness  1  19/209 (9.09%)  12/211 (5.69%) 
Dysgeusia  1  4/209 (1.91%)  13/211 (6.16%) 
Paraesthesia  1  4/209 (1.91%)  11/211 (5.21%) 
Psychiatric disorders     
Insomnia  1  8/209 (3.83%)  15/211 (7.11%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  34/209 (16.27%)  35/211 (16.59%) 
Oropharyngeal pain  1  19/209 (9.09%)  9/211 (4.27%) 
Epistaxis  1  15/209 (7.18%)  9/211 (4.27%) 
Dyspnoea  1  12/209 (5.74%)  16/211 (7.58%) 
Skin and subcutaneous tissue disorders     
Rash  1  48/209 (22.97%)  46/211 (21.80%) 
Dry skin  1  19/209 (9.09%)  28/211 (13.27%) 
Pruritus  1  17/209 (8.13%)  26/211 (12.32%) 
Dermatitis acneiform  1  16/209 (7.66%)  7/211 (3.32%) 
Alopecia  1  15/209 (7.18%)  55/211 (26.07%) 
Erythema  1  11/209 (5.26%)  13/211 (6.16%) 
Hyperhidrosis  1  11/209 (5.26%)  9/211 (4.27%) 
Night sweats  1  11/209 (5.26%)  2/211 (0.95%) 
Rash maculo-papular  1  11/209 (5.26%)  8/211 (3.79%) 
Actinic keratosis  1  8/209 (3.83%)  12/211 (5.69%) 
Palmar-plantar erythrodysaesthesia syndrome  1  8/209 (3.83%)  39/211 (18.48%) 
Hyperkeratosis  1  7/209 (3.35%)  68/211 (32.23%) 
Palmoplantar keratoderma  1  2/209 (0.96%)  23/211 (10.90%) 
Hair texture abnormal  1  0/209 (0.00%)  14/211 (6.64%) 
Vascular disorders     
Hypertension  1  45/209 (21.53%)  29/211 (13.74%) 
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
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01584648     History of Changes
Other Study ID Numbers: 115306
First Submitted: April 23, 2012
First Posted: April 25, 2012
Results First Submitted: April 10, 2014
Results First Posted: August 15, 2014
Last Update Posted: April 25, 2019