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Trial record 63 of 508 for:    melanoma phase III

A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma (coBRIM)

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: NCT01689519
Recruitment Status : Active, not recruiting
First Posted : September 21, 2012
Results First Posted : October 30, 2015
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Malignant Melanoma
Interventions Drug: Placebo
Drug: Vemurafenib
Drug: Cobimetinib
Enrollment 495
Recruitment Details  
Pre-assignment Details Written informed consent for participation in the study was obtained before performing any study-specific screening tests or evaluations.
Arm/Group Title Placebo + Vemurafenib Cobimetinib + Vemurafenib
Hide Arm/Group Description Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest. Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Period Title: Overall Study
Started 248 247
Received Treatment 247 246
Completed 82 109
Not Completed 166 138
Reason Not Completed
Death             143             116
Lost to Follow-up             6             2
Withdrawal by Subject             17             17
Physician Decision             0             3
Arm/Group Title Placebo + Vemurafenib Cobimetinib + Vemurafenib Total
Hide Arm/Group Description Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest. Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest. Total of all reporting groups
Overall Number of Baseline Participants 248 247 495
Hide Baseline Analysis Population Description
Intent-to-treat population: All randomized participants regardless of whether or not study treatment was received.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 248 participants 247 participants 495 participants
55.3  (13.8) 54.9  (14.0) 55.1  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 248 participants 247 participants 495 participants
Female
108
  43.5%
101
  40.9%
209
  42.2%
Male
140
  56.5%
146
  59.1%
286
  57.8%
1.Primary Outcome
Title Progression-free Survival
Hide Description Progression-free survival was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using Response Evaluation Criteria in Solid Tumors v1.1, or death from any cause, whichever came first. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Time Frame Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.
Arm/Group Title Placebo + Vemurafenib Cobimetinib + Vemurafenib
Hide Arm/Group Description:
Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed 248 247
Median (95% Confidence Interval)
Unit of Measure: Months
6.21
(5.55 to 7.39)
9.89 [1] 
(9.00 to NA)
[1]
NA = not estimable, could not be calculated due to too few events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Vemurafenib, Cobimetinib + Vemurafenib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The analysis was stratified by geographic region and metastasis classification (disease stage).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.512
Confidence Interval (2-Sided) 95%
0.387 to 0.679
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time from randomization until the date of death from any cause.
Time Frame Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.
Arm/Group Title Placebo + Vemurafenib Cobimetinib + Vemurafenib
Hide Arm/Group Description:
Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed 248 247
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
NA = not estimable, could not be calculated due to too few events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Vemurafenib, Cobimetinib + Vemurafenib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0463
Comments The analysis was stratified by geographic region and metastasis classification (disease stage).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.645
Confidence Interval (2-Sided) 95%
0.417 to 0.996
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With an Objective Response
Hide Description An objective response was defined as a complete response or a partial response determined on two consecutive occasions ≥ 4 weeks apart. Responses were determined by Response Evaluation Criteria in Solid Tumors v1.1. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.
Time Frame Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.
Arm/Group Title Placebo + Vemurafenib Cobimetinib + Vemurafenib
Hide Arm/Group Description:
Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed 248 247
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
44.8
(38.46 to 51.18)
67.6
(61.39 to 73.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Vemurafenib, Cobimetinib + Vemurafenib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 22.85
Confidence Interval (2-Sided) 95%
14.13 to 31.58
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was defined as the time from first occurrence of a documented confirmed objective response until the time of disease progression, as determined by investigator review of tumor assessments using Response Evaluation Criteria in Solid Tumors v1.1 or death from any cause during the study. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Time Frame Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received. Only participants with an objective response were included in the analysis.
Arm/Group Title Placebo + Vemurafenib Cobimetinib + Vemurafenib
Hide Arm/Group Description:
Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed 111 167
Median (95% Confidence Interval)
Unit of Measure: Months
7.29 [1] 
(5.78 to NA)
NA [1] 
(9.30 to NA)
[1]
NA = not estimable, could not be calculated due to too few events.
5.Secondary Outcome
Title Overall Survival (Final Analysis)
Hide Description Overall survival was defined as the time from randomization until the date of death from any cause.
Time Frame Baseline to the 28 August 2015 Overall Survival data cut-off (up to 2 years, 8 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.
Arm/Group Title Placebo + Vemurafenib Cobimetinib + Vemurafenib
Hide Arm/Group Description:
Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
Overall Number of Participants Analyzed 248 247
Median (95% Confidence Interval)
Unit of Measure: Months
17.38
(15.01 to 19.81)
22.28 [1] 
(20.27 to NA)
[1]
NA = not estimable, could not be calculated due to too few events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo + Vemurafenib, Cobimetinib + Vemurafenib
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0050
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.702
Confidence Interval (2-Sided) 95%
0.548 to 0.899
Estimation Comments The analysis was stratified by geographic region and metastasis classification (disease stage).
Time Frame Adverse events were collected from the time of each participant’s randomization into the study until their last visit until 28 days after the last dose of study drug (Safety data cut-off: 30 September 2015; up to 2 years, 9 months).
Adverse Event Reporting Description Safety population: All participants who received at least 1 dose of study treatment (ie, cobimetinib/placebo or vemurafenib).
 
Arm/Group Title Placebo + Vemurafenib Cobimetinib + Vemurafenib
Hide Arm/Group Description Participants received placebo orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest. Participants received cobimetinib 60 mg orally once daily on Days 1-21 of each 28 day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28 day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.
All-Cause Mortality
Placebo + Vemurafenib Cobimetinib + Vemurafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + Vemurafenib Cobimetinib + Vemurafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   69/246 (28.05%)   92/247 (37.25%) 
Blood and lymphatic system disorders     
Anaemia  1  1/246 (0.41%)  0/247 (0.00%) 
Cardiac disorders     
Acute coronary syndrome  1  0/246 (0.00%)  1/247 (0.40%) 
Atrial fibrillation  1  1/246 (0.41%)  4/247 (1.62%) 
Cardiac arrest  1  0/246 (0.00%)  1/247 (0.40%) 
Cardiac failure  1  1/246 (0.41%)  1/247 (0.40%) 
Cardiac tamponade  1  1/246 (0.41%)  0/247 (0.00%) 
Myocardial infarction  1  0/246 (0.00%)  1/247 (0.40%) 
Pericardial effusion  1  4/246 (1.63%)  0/247 (0.00%) 
Supraventricular tachycardia  1  1/246 (0.41%)  0/247 (0.00%) 
Tachycardia  1  1/246 (0.41%)  1/247 (0.40%) 
Endocrine disorders     
Hyperthyroidism  1  0/246 (0.00%)  1/247 (0.40%) 
Eye disorders     
Chorioretinopathy  1  0/246 (0.00%)  3/247 (1.21%) 
Iridocyclitis  1  1/246 (0.41%)  0/247 (0.00%) 
Retinal detachment  1  0/246 (0.00%)  4/247 (1.62%) 
Uveitis  1  1/246 (0.41%)  0/247 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/246 (0.41%)  1/247 (0.40%) 
Aphthous ulcer  1  0/246 (0.00%)  1/247 (0.40%) 
Colitis  1  0/246 (0.00%)  1/247 (0.40%) 
Constipation  1  0/246 (0.00%)  1/247 (0.40%) 
Diarrhoea  1  0/246 (0.00%)  3/247 (1.21%) 
Diverticular perforation  1  1/246 (0.41%)  0/247 (0.00%) 
Dysphagia  1  1/246 (0.41%)  0/247 (0.00%) 
Gastric antral vascular ectasia  1  0/246 (0.00%)  1/247 (0.40%) 
Gastrointestinal haemorrhage  1  0/246 (0.00%)  1/247 (0.40%) 
Gastrooesophageal reflux disease  1  1/246 (0.41%)  0/247 (0.00%) 
Intestinal obstruction  1  1/246 (0.41%)  0/247 (0.00%) 
Intestinal perforation  1  0/246 (0.00%)  1/247 (0.40%) 
Melaena  1  1/246 (0.41%)  0/247 (0.00%) 
Obstruction gastric  1  0/246 (0.00%)  1/247 (0.40%) 
Pancreatitis  1  2/246 (0.81%)  1/247 (0.40%) 
Periodontal disease  1  1/246 (0.41%)  0/247 (0.00%) 
Rectal polyp  1  1/246 (0.41%)  0/247 (0.00%) 
Small intestinal obstruction  1  0/246 (0.00%)  3/247 (1.21%) 
Vomiting  1  1/246 (0.41%)  2/247 (0.81%) 
General disorders     
Asthenia  1  0/246 (0.00%)  1/247 (0.40%) 
Death  1  1/246 (0.41%)  1/247 (0.40%) 
Fatigue  1  0/246 (0.00%)  1/247 (0.40%) 
Malaise  1  0/246 (0.00%)  1/247 (0.40%) 
Pyrexia  1  3/246 (1.22%)  6/247 (2.43%) 
Hepatobiliary disorders     
Cholecystitis  1  2/246 (0.81%)  0/247 (0.00%) 
Drug-induced liver injury  1  0/246 (0.00%)  1/247 (0.40%) 
Immune system disorders     
Hypersensitivity  1  0/246 (0.00%)  3/247 (1.21%) 
Sarcoidosis  1  0/246 (0.00%)  1/247 (0.40%) 
Infections and infestations     
Anal abscess  1  0/246 (0.00%)  1/247 (0.40%) 
Arthritis bacterial  1  1/246 (0.41%)  0/247 (0.00%) 
Cellulitis  1  0/246 (0.00%)  1/247 (0.40%) 
Clostridium difficile colitis  1  0/246 (0.00%)  1/247 (0.40%) 
Clostridium difficile infection  1  0/246 (0.00%)  1/247 (0.40%) 
Device related infection  1  0/246 (0.00%)  1/247 (0.40%) 
Diverticulitis  1  2/246 (0.81%)  1/247 (0.40%) 
Enterococcal sepsis  1  0/246 (0.00%)  1/247 (0.40%) 
Erysipelas  1  2/246 (0.81%)  1/247 (0.40%) 
Gastroenteritis  1  1/246 (0.41%)  1/247 (0.40%) 
Gastroenteritis clostridial  1  1/246 (0.41%)  0/247 (0.00%) 
Gastroenteritis viral  1  1/246 (0.41%)  0/247 (0.00%) 
Gastrointestinal bacterial infection  1  0/246 (0.00%)  1/247 (0.40%) 
Genitourinary tract infection  1  1/246 (0.41%)  0/247 (0.00%) 
Groin abscess  1  0/246 (0.00%)  1/247 (0.40%) 
Infection  1  0/246 (0.00%)  1/247 (0.40%) 
Pneumonia  1  3/246 (1.22%)  4/247 (1.62%) 
Sepsis  1  2/246 (0.81%)  1/247 (0.40%) 
Septic shock  1  0/246 (0.00%)  1/247 (0.40%) 
Tuberculosis  1  0/246 (0.00%)  1/247 (0.40%) 
Urinary tract infection  1  1/246 (0.41%)  1/247 (0.40%) 
Vulval cellulitis  1  0/246 (0.00%)  1/247 (0.40%) 
Wound infection  1  0/246 (0.00%)  1/247 (0.40%) 
Injury, poisoning and procedural complications     
Facial bones fracture  1  0/246 (0.00%)  1/247 (0.40%) 
Fall  1  0/246 (0.00%)  2/247 (0.81%) 
Femoral neck fracture  1  1/246 (0.41%)  1/247 (0.40%) 
Laceration  1  0/246 (0.00%)  1/247 (0.40%) 
Overdose  1  1/246 (0.41%)  0/247 (0.00%) 
Rib fracture  1  1/246 (0.41%)  1/247 (0.40%) 
Thoracic vertebral fracture  1  1/246 (0.41%)  0/247 (0.00%) 
Traumatic haematoma  1  0/246 (0.00%)  1/247 (0.40%) 
Upper limb fracture  1  1/246 (0.41%)  0/247 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  2/246 (0.81%)  4/247 (1.62%) 
Aspartate aminotransferase increased  1  2/246 (0.81%)  3/247 (1.21%) 
Blood alkaline phosphatase increased  1  1/246 (0.41%)  1/247 (0.40%) 
Blood creatine phosphokinase increased  1  0/246 (0.00%)  2/247 (0.81%) 
Blood creatinine increased  1  0/246 (0.00%)  1/247 (0.40%) 
Ejection fraction decreased  1  1/246 (0.41%)  1/247 (0.40%) 
Electrocardiogram qt prolonged  1  1/246 (0.41%)  0/247 (0.00%) 
Electrocardiogram T wave abnormal  1  0/246 (0.00%)  1/247 (0.40%) 
Gamma-glutamyltransferase increased  1  1/246 (0.41%)  2/247 (0.81%) 
Haemoglobin decreased  1  0/246 (0.00%)  1/247 (0.40%) 
Lipase increased  1  0/246 (0.00%)  1/247 (0.40%) 
Liver function test abnormal  1  1/246 (0.41%)  1/247 (0.40%) 
Metabolism and nutrition disorders     
Dehydration  1  0/246 (0.00%)  5/247 (2.02%) 
Diabetes mellitus  1  0/246 (0.00%)  1/247 (0.40%) 
Hypokalaemia  1  1/246 (0.41%)  0/247 (0.00%) 
Hyponatraemia  1  0/246 (0.00%)  1/247 (0.40%) 
Type 2 diabetes mellitus  1  0/246 (0.00%)  1/247 (0.40%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/246 (0.41%)  0/247 (0.00%) 
Arthritis  1  1/246 (0.41%)  0/247 (0.00%) 
Back pain  1  1/246 (0.41%)  0/247 (0.00%) 
Bursitis  1  0/246 (0.00%)  1/247 (0.40%) 
Muscular weakness  1  1/246 (0.41%)  0/247 (0.00%) 
Musculoskeletal chest pain  1  0/246 (0.00%)  1/247 (0.40%) 
Musculoskeletal pain  1  0/246 (0.00%)  1/247 (0.40%) 
Myalgia  1  1/246 (0.41%)  1/247 (0.40%) 
Pathological fracture  1  0/246 (0.00%)  1/247 (0.40%) 
Polyarthritis  1  1/246 (0.41%)  0/247 (0.00%) 
Rhabdomyolysis  1  1/246 (0.41%)  1/247 (0.40%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acanthoma  1  1/246 (0.41%)  0/247 (0.00%) 
Adenocarcinoma of colon  1  1/246 (0.41%)  0/247 (0.00%) 
Benign neoplasm  1  1/246 (0.41%)  0/247 (0.00%) 
Gastrointestinal tract adenoma  1  1/246 (0.41%)  0/247 (0.00%) 
Kaposi’s sarcoma  1  1/246 (0.41%)  0/247 (0.00%) 
Keratoacanthoma  1  4/246 (1.63%)  0/247 (0.00%) 
Lung adenocarcinoma  1  1/246 (0.41%)  0/247 (0.00%) 
Mucinous breast carcinoma  1  1/246 (0.41%)  0/247 (0.00%) 
Papilloma  1  1/246 (0.41%)  0/247 (0.00%) 
Squamous cell carcinoma of skin  1  1/246 (0.41%)  0/247 (0.00%) 
Transitional cell carcinoma  1  0/246 (0.00%)  2/247 (0.81%) 
Tumour haemorrhage  1  1/246 (0.41%)  0/247 (0.00%) 
Tumour pain  1  1/246 (0.41%)  0/247 (0.00%) 
Nervous system disorders     
Cerebral haemorrhage  1  0/246 (0.00%)  1/247 (0.40%) 
Cerebrovascular accident  1  0/246 (0.00%)  2/247 (0.81%) 
Coma  1  0/246 (0.00%)  1/247 (0.40%) 
Dizziness  1  0/246 (0.00%)  1/247 (0.40%) 
Dysarthria  1  0/246 (0.00%)  1/247 (0.40%) 
Dysgeusia  1  1/246 (0.41%)  0/247 (0.00%) 
Facial paresis  1  0/246 (0.00%)  1/247 (0.40%) 
Generalised tonic-clonic seizure  1  1/246 (0.41%)  0/247 (0.00%) 
Headache  1  1/246 (0.41%)  0/247 (0.00%) 
Hemiparesis  1  0/246 (0.00%)  1/247 (0.40%) 
Hydrocephalus  1  1/246 (0.41%)  0/247 (0.00%) 
Ischaemic stroke  1  0/246 (0.00%)  1/247 (0.40%) 
Myasthenia gravis  1  0/246 (0.00%)  1/247 (0.40%) 
Paraesthesia  1  1/246 (0.41%)  0/247 (0.00%) 
Polyneuropathy  1  0/246 (0.00%)  1/247 (0.40%) 
Seizure  1  0/246 (0.00%)  3/247 (1.21%) 
Subarachnoid haemorrhage  1  0/246 (0.00%)  1/247 (0.40%) 
Syncope  1  0/246 (0.00%)  1/247 (0.40%) 
VIIth nerve paralysis  1  1/246 (0.41%)  2/247 (0.81%) 
Psychiatric disorders     
Mania  1  0/246 (0.00%)  1/247 (0.40%) 
Renal and urinary disorders     
Acute kidney injury  1  2/246 (0.81%)  3/247 (1.21%) 
Calculus ureteric  1  1/246 (0.41%)  0/247 (0.00%) 
Diabetic nephropathy  1  0/246 (0.00%)  1/247 (0.40%) 
Renal colic  1  0/246 (0.00%)  1/247 (0.40%) 
Reproductive system and breast disorders     
Cervical polyp  1  1/246 (0.41%)  0/247 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Atelectasis  1  1/246 (0.41%)  0/247 (0.00%) 
Interstitial lung disease  1  0/246 (0.00%)  1/247 (0.40%) 
Pleural effusion  1  3/246 (1.22%)  0/247 (0.00%) 
Pneumonitis  1  0/246 (0.00%)  1/247 (0.40%) 
Pulmonary embolism  1  1/246 (0.41%)  1/247 (0.40%) 
Pulmonary haemorrhage  1  1/246 (0.41%)  0/247 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis exfoliative  1  2/246 (0.81%)  0/247 (0.00%) 
Drug reaction with eosinophilia and systemic symptoms  1  1/246 (0.41%)  1/247 (0.40%) 
Erythema multiforme  1  1/246 (0.41%)  0/247 (0.00%) 
Erythema nodosum  1  1/246 (0.41%)  0/247 (0.00%) 
Hyperkeratosis  1  1/246 (0.41%)  0/247 (0.00%) 
Panniculitis  1  0/246 (0.00%)  1/247 (0.40%) 
Rash  1  1/246 (0.41%)  4/247 (1.62%) 
Rash generalised  1  0/246 (0.00%)  1/247 (0.40%) 
Rash macular  1  0/246 (0.00%)  1/247 (0.40%) 
Rash maculo−papular  1  2/246 (0.81%)  3/247 (1.21%) 
Rash morbilliform  1  0/246 (0.00%)  1/247 (0.40%) 
Urticaria  1  0/246 (0.00%)  1/247 (0.40%) 
Vascular disorders     
Hypertension  1  0/246 (0.00%)  1/247 (0.40%) 
Hypertensive crisis  1  0/246 (0.00%)  1/247 (0.40%) 
Subgaleal haematoma  1  0/246 (0.00%)  1/247 (0.40%) 
Vasculitis  1  0/246 (0.00%)  1/247 (0.40%) 
Venous thrombosis limb  1  0/246 (0.00%)  1/247 (0.40%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Vemurafenib Cobimetinib + Vemurafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   235/246 (95.53%)   238/247 (96.36%) 
Blood and lymphatic system disorders     
Anaemia  1  20/246 (8.13%)  39/247 (15.79%) 
Eye disorders     
Chorioretinopathy  1  1/246 (0.41%)  29/247 (11.74%) 
Retinal detachment  1  1/246 (0.41%)  19/247 (7.69%) 
Vision blurred  1  6/246 (2.44%)  28/247 (11.34%) 
Gastrointestinal disorders     
Abdominal pain  1  18/246 (7.32%)  26/247 (10.53%) 
Abdominal pain upper  1  17/246 (6.91%)  12/247 (4.86%) 
Constipation  1  28/246 (11.38%)  26/247 (10.53%) 
Diarrhoea  1  82/246 (33.33%)  149/247 (60.32%) 
Dyspepsia  1  14/246 (5.69%)  19/247 (7.69%) 
Nausea  1  64/246 (26.02%)  105/247 (42.51%) 
Stomatitis  1  3/246 (1.22%)  15/247 (6.07%) 
Vomiting  1  33/246 (13.41%)  63/247 (25.51%) 
General disorders     
Asthenia  1  43/246 (17.48%)  46/247 (18.62%) 
Chills  1  13/246 (5.28%)  25/247 (10.12%) 
Fatigue  1  82/246 (33.33%)  91/247 (36.84%) 
Oedema peripheral  1  28/246 (11.38%)  34/247 (13.77%) 
Pyrexia  1  57/246 (23.17%)  69/247 (27.94%) 
Infections and infestations     
Conjunctivitis  1  5/246 (2.03%)  16/247 (6.48%) 
Folliculitis  1  12/246 (4.88%)  18/247 (7.29%) 
Nasopharyngitis  1  14/246 (5.69%)  20/247 (8.10%) 
Urinary tract infection  1  10/246 (4.07%)  15/247 (6.07%) 
Injury, poisoning and procedural complications     
Sunburn  1  45/246 (18.29%)  37/247 (14.98%) 
Investigations     
Alanine aminotransferase increased  1  43/246 (17.48%)  62/247 (25.10%) 
Aspartate aminotransferase increased  1  29/246 (11.79%)  58/247 (23.48%) 
Blood alkaline phosphatase increased  1  24/246 (9.76%)  41/247 (16.60%) 
Blood bilirubin increased  1  17/246 (6.91%)  19/247 (7.69%) 
Blood cholesterol increased  1  10/246 (4.07%)  16/247 (6.48%) 
Blood creatine phosphokinase increased  1  7/246 (2.85%)  86/247 (34.82%) 
Blood creatinine increased  1  20/246 (8.13%)  37/247 (14.98%) 
Ejection fraction decreased  1  12/246 (4.88%)  28/247 (11.34%) 
Gamma-glutamyltransferase increased  1  44/246 (17.89%)  52/247 (21.05%) 
Weight decreased  1  13/246 (5.28%)  16/247 (6.48%) 
Metabolism and nutrition disorders     
Decreased appetite  1  50/246 (20.33%)  50/247 (20.24%) 
Hyponatraemia  1  3/246 (1.22%)  13/247 (5.26%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  103/246 (41.87%)  94/247 (38.06%) 
Back pain  1  14/246 (5.69%)  19/247 (7.69%) 
Musculoskeletal pain  1  16/246 (6.50%)  11/247 (4.45%) 
Myalgia  1  31/246 (12.60%)  36/247 (14.57%) 
Pain in extremity  1  39/246 (15.85%)  29/247 (11.74%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  6/246 (2.44%)  15/247 (6.07%) 
Keratoacanthoma  1  20/246 (8.13%)  4/247 (1.62%) 
Melanocytic naevus  1  20/246 (8.13%)  5/247 (2.02%) 
Seborrhoeic keratosis  1  20/246 (8.13%)  15/247 (6.07%) 
Skin papilloma  1  31/246 (12.60%)  17/247 (6.88%) 
Squamous cell carcinoma of skin  1  31/246 (12.60%)  10/247 (4.05%) 
Nervous system disorders     
Dizziness  1  8/246 (3.25%)  15/247 (6.07%) 
Dysgeusia  1  25/246 (10.16%)  38/247 (15.38%) 
Headache  1  39/246 (15.85%)  44/247 (17.81%) 
Psychiatric disorders     
Anxiety  1  10/246 (4.07%)  13/247 (5.26%) 
Insomnia  1  24/246 (9.76%)  17/247 (6.88%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  31/246 (12.60%)  23/247 (9.31%) 
Dyspnoea  1  18/246 (7.32%)  19/247 (7.69%) 
Oropharyngeal pain  1  21/246 (8.54%)  18/247 (7.29%) 
Skin and subcutaneous tissue disorders     
Actinic keratosis  1  25/246 (10.16%)  13/247 (5.26%) 
Alopecia  1  75/246 (30.49%)  41/247 (16.60%) 
Dermatitis acneiform  1  22/246 (8.94%)  34/247 (13.77%) 
Dry skin  1  41/246 (16.67%)  38/247 (15.38%) 
Erythema  1  33/246 (13.41%)  26/247 (10.53%) 
Hyperkeratosis  1  66/246 (26.83%)  25/247 (10.12%) 
Keratosis pilaris  1  26/246 (10.57%)  9/247 (3.64%) 
Palmar-plantar erythrodysaesthesia syndrome  1  9/246 (3.66%)  17/247 (6.88%) 
Palmoplantar keratoderma  1  20/246 (8.13%)  5/247 (2.02%) 
Photosensitivity reaction  1  48/246 (19.51%)  84/247 (34.01%) 
Pruritus  1  47/246 (19.11%)  49/247 (19.84%) 
Rash  1  94/246 (38.21%)  98/247 (39.68%) 
Rash maculo-papular  1  37/246 (15.04%)  36/247 (14.57%) 
Solar dermatitis  1  13/246 (5.28%)  15/247 (6.07%) 
Vascular disorders     
Hypertension  1  20/246 (8.13%)  38/247 (15.38%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01689519     History of Changes
Other Study ID Numbers: GO28141
2012-003008-11 ( EudraCT Number )
First Submitted: September 18, 2012
First Posted: September 21, 2012
Results First Submitted: July 1, 2015
Results First Posted: October 30, 2015
Last Update Posted: April 17, 2019