Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma (COMBI-v)

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: NCT01597908
Recruitment Status : Completed
First Posted : May 14, 2012
Results First Posted : December 4, 2014
Last Update Posted : May 21, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Interventions Drug: Dabrafenib
Drug: Vemurafenib
Drug: Trametinib
Enrollment 704
Recruitment Details  
Pre-assignment Details Participants (par.) were stratified for lactate dehydrogenase (LDH) and BRAF mutation (V600E versus V600K). Par. were randomized in a 1:1 ratio to receive either dabrafenib and trametinib combination therapy or vemurafenib until disease progression, death, or withdrawal.
Arm/Group Title Dabrafenib Plus Trametinib Vemurafenib
Hide Arm/Group Description Participants received dabrafenib 150 milligrams (mg) orally twice daily (BID) and trametinib 2 mg orally once daily. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor. Participants received vemurafenib 960 mg orally BID. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Period Title: Overall Study
Started 352 352
Ongoing 236 202
Completed 0 0
Not Completed 352 352
Reason Not Completed
Death             100             122
Lost to Follow-up             4             9
Physician Decision             2             1
Withdrawal by Subject             10             18
Ongoing             236             202
Arm/Group Title Dabrafenib Plus Trametinib Vemurafenib Total
Hide Arm/Group Description Participants received dabrafenib 150 mg orally BID and trametinib 2 mg orally once daily. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor. Participants received vemurafenib 960 mg orally BID. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor. Total of all reporting groups
Overall Number of Baseline Participants 352 352 704
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 352 participants 352 participants 704 participants
55.0
(18 to 91)
54.0
(18 to 88)
54.5
(18 to 91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
Female
144
  40.9%
172
  48.9%
316
  44.9%
Male
208
  59.1%
180
  51.1%
388
  55.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 352 participants 352 participants 704 participants
Asian - East Asian Heritage 8 8 16
White - Arabic/North African Heritage 4 2 6
White - White/Caucasian/European Heritage 339 339 678
White - Mixed Race 1 0 1
Mixed Race 0 1 1
African American/African Heritage 0 1 1
American Indian or Alaskan Native 0 1 1
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the time from randomization until death due to any cause.
Time Frame From randomization until death due to any cause (up to Study Week 92)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all randomized participants, whether or not study medication was administered. All participants in the ITT Population were analyzed. For participants who did not die, time of death was censored at the date of last contact.
Arm/Group Title Dabrafenib Plus Trametinib Vemurafenib
Hide Arm/Group Description:
Participants received dabrafenib 150 mg orally BID and trametinib 2 mg orally once daily. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Participants received vemurafenib 960 mg orally BID. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Overall Number of Participants Analyzed 352 352
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(18.3 to NA)
17.2 [2] 
(16.4 to NA)
[1]
There were too few events of death to calculate the median or the upper limit of the confidence interval.
[2]
There were too few events of death to calculate the upper limit of the confidence interval.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabrafenib Plus Trametinib, Vemurafenib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Stratified log-rank test
Comments Stratification was by Baseline LDH and BRAF mutation status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.53 to 0.89
Estimation Comments Hazard ratios are estimated using a Pike estimator.
2.Secondary Outcome
Title Progression-free Survival, as Assessed by the Investigator
Hide Description Progression-free survival (PFS) is defined as the time from randomization to the first documented occurrence of disease progression or death due to any cause. PFS for investigator-assessed response was summarized per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, which is a set of published rules defining when cancer patients 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.
Time Frame From randomization to the first documented occurrence of disease progression or death due to any cause (up to Study Week 80)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants who did not progress or die or who progressed or died after the start of new anti-cancer therapy or after an extended period without adequate assessment were censored at their date of last adequate assessment prior to progression or death even if subsequent information was available regarding progression or death.
Arm/Group Title Dabrafenib Plus Trametinib Vemurafenib
Hide Arm/Group Description:
Participants received dabrafenib 150 mg orally BID and trametinib 2 mg orally once daily. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Participants received vemurafenib 960 mg orally BID. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Overall Number of Participants Analyzed 352 352
Median (95% Confidence Interval)
Unit of Measure: Months
11.4
(9.9 to 14.9)
7.3
(5.8 to 7.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabrafenib Plus Trametinib, Vemurafenib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Stratified log-rank test
Comments Stratification was by Baseline LDH and BRAF mutation status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.46 to 0.69
Estimation Comments Hazard ratios are estimated using a Pike estimator.
3.Secondary Outcome
Title Overall Response, as Assessed by the Investigator
Hide Description Overall response is defined as the number of responders (complete response [CR] + partial response [PR] per RECIST, Version 1.1) as summarized by Investigator assessment. CR is defined as the disappearance of all evidence of target lesions. PR is defined as at least a 30% reduction from Baseline in the sum of the longest diameter (LD) of all target lesions. Data are reported as those participants with measureable disease.
Time Frame Screening, Week 8 and every 8 weeks thereafter through Week 56, and then every 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title Dabrafenib Plus Trametinib Vemurafenib
Hide Arm/Group Description:
Participants received dabrafenib 150 mg orally BID and trametinib 2 mg orally once daily. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Participants received vemurafenib 960 mg orally BID. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Overall Number of Participants Analyzed 351 350
Measure Type: Number
Unit of Measure: Participants
226 180
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dabrafenib Plus Trametinib, Vemurafenib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage of responders
Estimated Value 13
Confidence Interval (2-Sided) 95%
5.7 to 20.2
Estimation Comments The difference in the percentage of participants (dabrafenib plus trametinib minus vemurafenib) with CR + PR was reported.
4.Secondary Outcome
Title Duration of Response, as Assessed by the Investigator
Hide Description Duration of response is defined as the time from the first documented evidence of a CR (disappearance of all evidence of target lesions) or a PR (at least a 30% reduction from Baseline in the sum of the longest diameter of all target lesions) until disease progression 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 at least1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. Data are summarized per RECIST, Version 1.1.
Time Frame From the first documented evidence of a CR or PR until the earliest date of disease progression or death due to any cause (up to Study Week 80)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with a confirmed response (CR and PR) were analyzed. Participants with measurable and non-measurable disease were analyzed.
Arm/Group Title Dabrafenib Plus Trametinib Vemurafenib
Hide Arm/Group Description:
Participants received dabrafenib 150 mg orally BID and trametinib 2 mg orally once daily. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Participants received vemurafenib 960 mg orally BID. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
Overall Number of Participants Analyzed 226 181
Median (95% Confidence Interval)
Unit of Measure: Months
13.8 [1] 
(11.0 to NA)
7.5
(7.3 to 9.3)
[1]
There were too few responses to calculate the upper limit of the confidence interval.
Time Frame Serious adverse events (SAEs) and non-serious AEs were collected from the time the first dose of study treatment was administered until 30 days after discontinuation of study treatment (up to Study Week 93).
Adverse Event Reporting Description SAEs and non-serious AEs are reported for the Safety Population, comprised of all participants who were administered at least one dose of investigational treatment.
 
Arm/Group Title Dabrafenib Plus Trametinib Vemurafenib
Hide Arm/Group Description Participants received dabrafenib 150 mg orally BID and trametinib 2 mg orally once daily. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor. Participants received vemurafenib 960 mg orally BID. Treatment continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Treatment beyond progression was allowed subject to consultation with the GlaxoSmithKline medical monitor.
All-Cause Mortality
Dabrafenib Plus Trametinib Vemurafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Dabrafenib Plus Trametinib Vemurafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   131/350 (37.43%)   122/349 (34.96%) 
Blood and lymphatic system disorders     
Anaemia  1  3/350 (0.86%)  2/349 (0.57%) 
Leukopenia  1  2/350 (0.57%)  1/349 (0.29%) 
Neutropenia  1  2/350 (0.57%)  0/349 (0.00%) 
Thrombocytopenia  1  2/350 (0.57%)  0/349 (0.00%) 
Febrile neutropenia  1  1/350 (0.29%)  1/349 (0.29%) 
Cardiac disorders     
Atrial fibrillation  1  2/350 (0.57%)  4/349 (1.15%) 
Arteriosclerosis coronary artery  1  1/350 (0.29%)  0/349 (0.00%) 
Myocardial infarction  1  1/350 (0.29%)  0/349 (0.00%) 
Acute coronary syndrome  1  0/350 (0.00%)  2/349 (0.57%) 
Angina unstable  1  0/350 (0.00%)  1/349 (0.29%) 
Pericarditis  1  0/350 (0.00%)  4/349 (1.15%) 
Supraventricular tachycardia  1  0/350 (0.00%)  1/349 (0.29%) 
Ear and labyrinth disorders     
Vertigo  1  1/350 (0.29%)  0/349 (0.00%) 
Eye disorders     
Chorioretinopathy  1  2/350 (0.57%)  1/349 (0.29%) 
Iridocyclitis  1  1/350 (0.29%)  0/349 (0.00%) 
Eye haemorrhage  1  0/350 (0.00%)  1/349 (0.29%) 
Retinal degeneration  1  0/350 (0.00%)  1/349 (0.29%) 
Retinal vein occlusion  1  0/350 (0.00%)  1/349 (0.29%) 
Gastrointestinal disorders     
Vomiting  1  7/350 (2.00%)  1/349 (0.29%) 
Nausea  1  4/350 (1.14%)  1/349 (0.29%) 
Diarrhoea  1  3/350 (0.86%)  0/349 (0.00%) 
Duodenal ulcer  1  2/350 (0.57%)  0/349 (0.00%) 
Duodenal ulcer haemorrhage  1  2/350 (0.57%)  0/349 (0.00%) 
Inguinal hernia  1  2/350 (0.57%)  0/349 (0.00%) 
Duodenal perforation  1  1/350 (0.29%)  0/349 (0.00%) 
Gastrointestinal hypomotility  1  1/350 (0.29%)  0/349 (0.00%) 
Gastrointestinal pain  1  1/350 (0.29%)  0/349 (0.00%) 
Abdominal pain  1  0/350 (0.00%)  1/349 (0.29%) 
Abdominal pain upper  1  0/350 (0.00%)  1/349 (0.29%) 
Constipation  1  0/350 (0.00%)  1/349 (0.29%) 
Gastric ulcer haemorrhage  1  0/350 (0.00%)  1/349 (0.29%) 
Ileus  1  0/350 (0.00%)  2/349 (0.57%) 
Large intestine perforation  1  0/350 (0.00%)  1/349 (0.29%) 
Pancreatitis  1  0/350 (0.00%)  1/349 (0.29%) 
General disorders     
Pyrexia  1  49/350 (14.00%)  6/349 (1.72%) 
Chills  1  13/350 (3.71%)  0/349 (0.00%) 
Asthenia  1  2/350 (0.57%)  0/349 (0.00%) 
Fatigue  1  2/350 (0.57%)  1/349 (0.29%) 
Influenza like illness  1  2/350 (0.57%)  0/349 (0.00%) 
Malaise  1  1/350 (0.29%)  0/349 (0.00%) 
General physical health deterioration  1  0/350 (0.00%)  1/349 (0.29%) 
Non-cardiac chest pain  1  0/350 (0.00%)  1/349 (0.29%) 
Hepatobiliary disorders     
Bile duct obstruction  1  1/350 (0.29%)  0/349 (0.00%) 
Hepatocellular injury  1  1/350 (0.29%)  0/349 (0.00%) 
Hypertransaminasaemia  1  1/350 (0.29%)  0/349 (0.00%) 
Cholecystitis  1  0/350 (0.00%)  1/349 (0.29%) 
Cholelithiasis  1  0/350 (0.00%)  1/349 (0.29%) 
Hepatitis  1  0/350 (0.00%)  1/349 (0.29%) 
Hepatotoxicity  1  0/350 (0.00%)  2/349 (0.57%) 
Immune system disorders     
Drug hypersensitivity  1  0/350 (0.00%)  1/349 (0.29%) 
Hypersensitivity  1  0/350 (0.00%)  1/349 (0.29%) 
Infections and infestations     
Urinary tract infection  1  6/350 (1.71%)  1/349 (0.29%) 
Erysipelas  1  4/350 (1.14%)  0/349 (0.00%) 
Cellulitis  1  3/350 (0.86%)  1/349 (0.29%) 
Gastrointestinal infection  1  2/350 (0.57%)  0/349 (0.00%) 
Infection  1  2/350 (0.57%)  0/349 (0.00%) 
Sepsis  1  2/350 (0.57%)  0/349 (0.00%) 
Abdominal sepsis  1  1/350 (0.29%)  0/349 (0.00%) 
Bacteraemia  1  1/350 (0.29%)  0/349 (0.00%) 
Biliary sepsis  1  1/350 (0.29%)  0/349 (0.00%) 
Enterocolitis infectious  1  1/350 (0.29%)  1/349 (0.29%) 
Escherichia sepsis  1  1/350 (0.29%)  0/349 (0.00%) 
Gastroenteritis  1  1/350 (0.29%)  0/349 (0.00%) 
Haematoma infection  1  1/350 (0.29%)  0/349 (0.00%) 
Helicobacter infection  1  1/350 (0.29%)  0/349 (0.00%) 
Kidney infection  1  1/350 (0.29%)  0/349 (0.00%) 
Lobar pneumonia  1  1/350 (0.29%)  0/349 (0.00%) 
Respiratory tract infection  1  1/350 (0.29%)  0/349 (0.00%) 
Staphylococcal abscess  1  1/350 (0.29%)  0/349 (0.00%) 
Urosepsis  1  1/350 (0.29%)  0/349 (0.00%) 
Viral infection  1  1/350 (0.29%)  0/349 (0.00%) 
Bronchopneumonia  1  0/350 (0.00%)  1/349 (0.29%) 
Enteritis infectious  1  0/350 (0.00%)  1/349 (0.29%) 
Lower respiratory tract infection  1  0/350 (0.00%)  1/349 (0.29%) 
Lung infection  1  0/350 (0.00%)  1/349 (0.29%) 
Meningitis  1  0/350 (0.00%)  1/349 (0.29%) 
Oesophageal candidiasis  1  0/350 (0.00%)  1/349 (0.29%) 
Pleural infection  1  0/350 (0.00%)  1/349 (0.29%) 
Pneumonia  1  0/350 (0.00%)  4/349 (1.15%) 
Sinusitis  1  0/350 (0.00%)  1/349 (0.29%) 
Superinfection  1  0/350 (0.00%)  1/349 (0.29%) 
Tonsillitis  1  0/350 (0.00%)  1/349 (0.29%) 
Injury, poisoning and procedural complications     
Radius fracture  1  1/350 (0.29%)  0/349 (0.00%) 
Subdural haematoma  1  1/350 (0.29%)  0/349 (0.00%) 
Femur fracture  1  0/350 (0.00%)  1/349 (0.29%) 
Radiation necrosis  1  0/350 (0.00%)  1/349 (0.29%) 
Toxicity to various agents  1  0/350 (0.00%)  1/349 (0.29%) 
Investigations     
Ejection fraction decreased  1  24/350 (6.86%)  0/349 (0.00%) 
Alanine aminotransferase increased  1  5/350 (1.43%)  8/349 (2.29%) 
Hepatic enzyme increased  1  4/350 (1.14%)  6/349 (1.72%) 
Aspartate aminotransferase increased  1  3/350 (0.86%)  5/349 (1.43%) 
Blood creatine phosphokinase increased  1  3/350 (0.86%)  0/349 (0.00%) 
Blood creatinine increased  1  2/350 (0.57%)  1/349 (0.29%) 
Blood bilirubin increased  1  1/350 (0.29%)  6/349 (1.72%) 
Troponin I increased  1  1/350 (0.29%)  0/349 (0.00%) 
Blood alkaline phosphatase increased  1  0/350 (0.00%)  2/349 (0.57%) 
International normalised ratio increased  1  0/350 (0.00%)  1/349 (0.29%) 
Metabolism and nutrition disorders     
Dehydration  1  8/350 (2.29%)  2/349 (0.57%) 
Hyponatraemia  1  5/350 (1.43%)  0/349 (0.00%) 
Hypercalcaemia  1  1/350 (0.29%)  0/349 (0.00%) 
Hyperglycaemia  1  1/350 (0.29%)  0/349 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  1/350 (0.29%)  0/349 (0.00%) 
Osteoarthritis  1  1/350 (0.29%)  0/349 (0.00%) 
Rhabdomyolysis  1  1/350 (0.29%)  0/349 (0.00%) 
Arthralgia  1  0/350 (0.00%)  1/349 (0.29%) 
Arthritis  1  0/350 (0.00%)  1/349 (0.29%) 
Pathological fracture  1  0/350 (0.00%)  1/349 (0.29%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  3/350 (0.86%)  3/349 (0.86%) 
Squamous cell carcinoma  1  3/350 (0.86%)  33/349 (9.46%) 
Acute myeloid leukaemia  1  1/350 (0.29%)  0/349 (0.00%) 
Benign neoplasm of adrenal gland  1  1/350 (0.29%)  0/349 (0.00%) 
Keratoacanthoma  1  1/350 (0.29%)  21/349 (6.02%) 
Lung adenocarcinoma  1  1/350 (0.29%)  0/349 (0.00%) 
Malignant melanoma  1  1/350 (0.29%)  4/349 (1.15%) 
Squamous cell carcinoma of skin  1  1/350 (0.29%)  17/349 (4.87%) 
Superficial spreading melanoma stage III  1  1/350 (0.29%)  0/349 (0.00%) 
Astrocytoma, low grade  1  0/350 (0.00%)  1/349 (0.29%) 
Bowen's disease  1  0/350 (0.00%)  1/349 (0.29%) 
Carcinoma in situ  1  0/350 (0.00%)  1/349 (0.29%) 
Lentigo maligna  1  0/350 (0.00%)  1/349 (0.29%) 
Lip squamous cell carcinoma  1  0/350 (0.00%)  1/349 (0.29%) 
Malignant melanoma in situ  1  0/350 (0.00%)  2/349 (0.57%) 
Metastases to central nervous system  1  0/350 (0.00%)  1/349 (0.29%) 
Metastatic malignant melanoma  1  0/350 (0.00%)  1/349 (0.29%) 
Skin papilloma  1  0/350 (0.00%)  1/349 (0.29%) 
Transitional cell carcinoma  1  0/350 (0.00%)  1/349 (0.29%) 
Nervous system disorders     
Cerebral haemorrhage  1  2/350 (0.57%)  1/349 (0.29%) 
Headache  1  2/350 (0.57%)  0/349 (0.00%) 
Brain stem haemorrhage  1  1/350 (0.29%)  0/349 (0.00%) 
Hepatic encephalopathy  1  1/350 (0.29%)  0/349 (0.00%) 
Syncope  1  1/350 (0.29%)  0/349 (0.00%) 
Cerebral ischaemia  1  0/350 (0.00%)  1/349 (0.29%) 
Cerebrovascular accident  1  0/350 (0.00%)  1/349 (0.29%) 
Dizziness  1  0/350 (0.00%)  1/349 (0.29%) 
Epilepsy  1  0/350 (0.00%)  1/349 (0.29%) 
Migraine  1  0/350 (0.00%)  1/349 (0.29%) 
Transient ischaemic attack  1  0/350 (0.00%)  1/349 (0.29%) 
Psychiatric disorders     
Mental status changes  1  1/350 (0.29%)  0/349 (0.00%) 
Confusional state  1  0/350 (0.00%)  1/349 (0.29%) 
Renal and urinary disorders     
Renal failure  1  4/350 (1.14%)  0/349 (0.00%) 
Nephritis  1  1/350 (0.29%)  0/349 (0.00%) 
Nephropathy toxic  1  1/350 (0.29%)  0/349 (0.00%) 
Renal failure acute  1  1/350 (0.29%)  1/349 (0.29%) 
Prerenal failure  1  0/350 (0.00%)  1/349 (0.29%) 
Reproductive system and breast disorders     
Ovarian cyst  1  1/350 (0.29%)  0/349 (0.00%) 
Uterine haemorrhage  1  0/350 (0.00%)  1/349 (0.29%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  4/350 (1.14%)  0/349 (0.00%) 
Dyspnoea  1  2/350 (0.57%)  2/349 (0.57%) 
Pneumonitis  1  2/350 (0.57%)  0/349 (0.00%) 
Cough  1  1/350 (0.29%)  0/349 (0.00%) 
Haemoptysis  1  1/350 (0.29%)  0/349 (0.00%) 
Asthma  1  0/350 (0.00%)  1/349 (0.29%) 
Interstitial lung disease  1  0/350 (0.00%)  1/349 (0.29%) 
Pulmonary oedema  1  0/350 (0.00%)  1/349 (0.29%) 
Skin and subcutaneous tissue disorders     
Purpura  1  2/350 (0.57%)  0/349 (0.00%) 
Rash  1  2/350 (0.57%)  3/349 (0.86%) 
Dermatitis  1  1/350 (0.29%)  0/349 (0.00%) 
Rash maculo-papular  1  1/350 (0.29%)  2/349 (0.57%) 
Actinic keratosis  1  0/350 (0.00%)  1/349 (0.29%) 
Dermatitis bullous  1  0/350 (0.00%)  1/349 (0.29%) 
Erythema  1  0/350 (0.00%)  1/349 (0.29%) 
Rash erythematous  1  0/350 (0.00%)  1/349 (0.29%) 
Skin lesion  1  0/350 (0.00%)  1/349 (0.29%) 
Vascular disorders     
Hypotension  1  5/350 (1.43%)  0/349 (0.00%) 
Deep vein thrombosis  1  1/350 (0.29%)  0/349 (0.00%) 
Haemorrhage  1  1/350 (0.29%)  0/349 (0.00%) 
Embolism  1  0/350 (0.00%)  1/349 (0.29%) 
Hypertension  1  0/350 (0.00%)  2/349 (0.57%) 
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 Plus Trametinib Vemurafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   332/350 (94.86%)   342/349 (97.99%) 
Blood and lymphatic system disorders     
Neutropenia  1  30/350 (8.57%)  4/349 (1.15%) 
Anaemia  1  23/350 (6.57%)  15/349 (4.30%) 
Gastrointestinal disorders     
Nausea  1  118/350 (33.71%)  125/349 (35.82%) 
Diarrhoea  1  112/350 (32.00%)  131/349 (37.54%) 
Vomiting  1  98/350 (28.00%)  53/349 (15.19%) 
Constipation  1  45/350 (12.86%)  22/349 (6.30%) 
Abdominal pain  1  30/350 (8.57%)  28/349 (8.02%) 
Abdominal pain upper  1  30/350 (8.57%)  32/349 (9.17%) 
Dry mouth  1  25/350 (7.14%)  6/349 (1.72%) 
General disorders     
Pyrexia  1  164/350 (46.86%)  70/349 (20.06%) 
Chills  1  103/350 (29.43%)  27/349 (7.74%) 
Fatigue  1  100/350 (28.57%)  114/349 (32.66%) 
Asthenia  1  54/350 (15.43%)  57/349 (16.33%) 
Oedema peripheral  1  42/350 (12.00%)  35/349 (10.03%) 
Influenza like illness  1  28/350 (8.00%)  14/349 (4.01%) 
Local swelling  1  24/350 (6.86%)  14/349 (4.01%) 
Infections and infestations     
Nasopharyngitis  1  40/350 (11.43%)  27/349 (7.74%) 
Urinary tract infection  1  18/350 (5.14%)  6/349 (1.72%) 
Folliculitis  1  13/350 (3.71%)  22/349 (6.30%) 
Conjunctivitis  1  9/350 (2.57%)  34/349 (9.74%) 
Injury, poisoning and procedural complications     
Sunburn  1  2/350 (0.57%)  50/349 (14.33%) 
Investigations     
Alanine aminotransferase increased  1  44/350 (12.57%)  53/349 (15.19%) 
Aspartate aminotransferase increased  1  37/350 (10.57%)  40/349 (11.46%) 
Gamma-glutamyltransferase increased  1  31/350 (8.86%)  33/349 (9.46%) 
Blood alkaline phosphatase increased  1  25/350 (7.14%)  27/349 (7.74%) 
Weight decreased  1  15/350 (4.29%)  41/349 (11.75%) 
Blood creatinine increased  1  12/350 (3.43%)  36/349 (10.32%) 
Metabolism and nutrition disorders     
Decreased appetite  1  42/350 (12.00%)  70/349 (20.06%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  84/350 (24.00%)  177/349 (50.72%) 
Myalgia  1  58/350 (16.57%)  51/349 (14.61%) 
Muscle spasms  1  34/350 (9.71%)  11/349 (3.15%) 
Pain in extremity  1  33/350 (9.43%)  41/349 (11.75%) 
Back pain  1  27/350 (7.71%)  23/349 (6.59%) 
Musculoskeletal pain  1  14/350 (4.00%)  24/349 (6.88%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin papilloma  1  6/350 (1.71%)  80/349 (22.92%) 
Nervous system disorders     
Headache  1  100/350 (28.57%)  77/349 (22.06%) 
Dizziness  1  34/350 (9.71%)  21/349 (6.02%) 
Dysgeusia  1  24/350 (6.86%)  46/349 (13.18%) 
Psychiatric disorders     
Insomnia  1  18/350 (5.14%)  31/349 (8.88%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  68/350 (19.43%)  34/349 (9.74%) 
Epistaxis  1  25/350 (7.14%)  3/349 (0.86%) 
Dyspnoea  1  23/350 (6.57%)  27/349 (7.74%) 
Oropharyngeal pain  1  22/350 (6.29%)  18/349 (5.16%) 
Skin and subcutaneous tissue disorders     
Rash  1  75/350 (21.43%)  148/349 (42.41%) 
Erythema  1  30/350 (8.57%)  39/349 (11.17%) 
Pruritus  1  30/350 (8.57%)  75/349 (21.49%) 
Dry skin  1  29/350 (8.29%)  62/349 (17.77%) 
Night sweats  1  23/350 (6.57%)  8/349 (2.29%) 
Dermatitis acneiform  1  22/350 (6.29%)  20/349 (5.73%) 
Alopecia  1  20/350 (5.71%)  137/349 (39.26%) 
Hyperkeratosis  1  15/350 (4.29%)  86/349 (24.64%) 
Photosensitivity reaction  1  13/350 (3.71%)  78/349 (22.35%) 
Rash maculo-papular  1  12/350 (3.43%)  26/349 (7.45%) 
Palmar-plantar erythrodysaesthesia syndrome  1  8/350 (2.29%)  55/349 (15.76%) 
Palmoplantar keratoderma  1  6/350 (1.71%)  40/349 (11.46%) 
Actinic keratosis  1  5/350 (1.43%)  24/349 (6.88%) 
Keratosis pilaris  1  4/350 (1.14%)  44/349 (12.61%) 
Vascular disorders     
Hypertension  1  92/350 (26.29%)  83/349 (23.78%) 
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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Clinical Disclosure Office
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: NCT01597908     History of Changes
Other Study ID Numbers: 116513
CDRB436B2302 ( Other Identifier: Novartis )
First Submitted: May 10, 2012
First Posted: May 14, 2012
Results First Submitted: December 1, 2014
Results First Posted: December 4, 2014
Last Update Posted: May 21, 2019