Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 : Completed
First Posted : September 21, 2012
Results First Posted : October 30, 2015
Last Update Posted : September 16, 2020
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 Cobimetinib + Vemurafenib Placebo + Vemurafenib
Hide Arm/Group Description 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. 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.
Period Title: Intent to Treat
Started 247 248
Completed 0 0
Not Completed 247 248
Reason Not Completed
Death             157             167
Lost to Follow-up             4             8
Other             2             4
Physician Decision             4             1
Study terminated by Spon6sor             59             48
Withdrawal by Subject             21             20
Period Title: Safety Population
Started 248 245
Completed 0 0
Not Completed 248 245
Reason Not Completed
Death             158             165
Lost to Follow-up             4             8
Other             2             4
Physician Decision             4             1
Study Terminated By Sponsor             60             47
Withdrawal by Subject             20             20
Arm/Group Title Cobimetinib + Vemurafenib Placebo + Vemurafenib Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 247 248 495
Hide Baseline Analysis Population Description
Intent-to-treat population: All randomized participants, regardless of whether or not study treatment was received.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 248 participants 495 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
183
  74.1%
179
  72.2%
362
  73.1%
>=65 years
64
  25.9%
69
  27.8%
133
  26.9%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 247 participants 248 participants 495 participants
54.9  (14.0) 55.3  (13.8) 55.1  (13.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 247 participants 248 participants 495 participants
Female
101
  40.9%
108
  43.5%
209
  42.2%
Male
146
  59.1%
140
  56.5%
286
  57.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Count of Participants
Number Analyzed 247 participants 248 participants 495 participants
Asian 1 0 1
More than one race 1 1 2
Native Hawaiian or other Pacific Islande 0 1 1
Black or African American 0 0 0
White 227 235 462
Unknown or Not Reported 16 9 25
Other 2 2 4
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Count of Participants
Number Analyzed 247 participants 248 participants 495 participants
Hispanic or Latino 14 12 26
Not Hispanic or Latino 213 223 436
Not Stated 16 10 26
Unknown 4 3 7
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 21 July 2019 data cut-off (up to 7 years, 6 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 Cobimetinib + Vemurafenib Placebo + Vemurafenib
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 247 248
Median (95% Confidence Interval)
Unit of Measure: Months
Primary Analysis: 9 May 2014
9.90 [1] 
(9.00 to NA)
6.20
(5.55 to 7.39)
Post hoc Efficacy Analysis: 16 January 2015
12.30
(9.50 to 13.40)
7.20
(5.60 to 7.50)
Extended 5-Year Analysis: 21 July 2019
12.60
(9.50 to 14.80)
7.20
(5.60 to 7.50)
[1]
NA = not estimable, could not be calculated due to too few events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Primary Analysis 9 May 2014
Type of Statistical Test Superiority or Other (legacy)
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 0.51
Confidence Interval (2-Sided) 95%
0.39 to 0.68
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Post hoc Efficacy Analysis: 16 January 2015
Type of Statistical Test Superiority or Other (legacy)
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 0.58
Confidence Interval (2-Sided) 95%
0.46 to 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Extended 5-Year Analysis: 21 July 2019
Type of Statistical Test Superiority or Other (legacy)
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 0.65
Confidence Interval (2-Sided) 95%
0.53 to 0.79
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 21 July 2019 data cut-off (up to 7 years, 6 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 Cobimetinib + Vemurafenib Placebo + Vemurafenib
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 247 248
Median (95% Confidence Interval)
Unit of Measure: Months
Primary Analysis 9 May 2014
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Post hoc Analysis 16 January 2015
NA [1] 
(20.70 to NA)
17.00 [1] 
(15.00 to NA)
Final Analysis 28 August 2015
22.30 [1] 
(20.3 to NA)
17.40
(15.00 to 19.8)
Extended 5-year Analysis 21 July 2019
22.50
(20.30 to 28.80)
17.40
(15.00 to 19.80)
[1]
NA = not estimable, could not be calculated due to too few events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Primary Analysis 9 May 2014
Type of Statistical Test Superiority or Other (legacy)
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%
0.42 to 1.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Post hoc Analysis 16 January 2015
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
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 0.65
Confidence Interval (2-Sided) 95%
0.49 to 0.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Final Analysis 28 August 2015
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0050
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 0.70
Confidence Interval (2-Sided) 95%
0.55 to 0.90
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 21 July 2019 data cut-off (up to 7 years, 6 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 Cobimetinib + Vemurafenib Placebo + Vemurafenib
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 247 248
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Primary Analysis: 9 May 2014
67.60
(61.39 to 73.41)
44.80
(38.46 to 51.18)
Post hoc Efficacy Analysis: 16 January 2015
69.60
(63.50 to 75.30)
50.00
(43.60 to 56.40)
Extended 5-Year Analysis: 21 July 2019
69.60
(63.49 to 75.31)
49.60
(43.21 to 55.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Primary Analysis: 9 May 2014
Type of Statistical Test Superiority or Other (legacy)
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]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Post hoc Efficacy Analysis: 16 January 2015
Type of Statistical Test Superiority or Other (legacy)
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 19.6
Confidence Interval (2-Sided) 95%
11.0 to 28.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobimetinib + Vemurafenib, Placebo + Vemurafenib
Comments Extended 5-Year Analysis: 21 July 2019
Type of Statistical Test Superiority or Other (legacy)
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 20.00
Confidence Interval (2-Sided) 95%
11.40 to 28.70
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 21 July 2019 data cut-off (up to 7 years, 6 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 Cobimetinib + Vemurafenib Placebo + Vemurafenib
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 247 248
Median (95% Confidence Interval)
Unit of Measure: Months
Primary Analysis: 9 May 2014 Number Analyzed 247 participants 248 participants
NA [1] 
(9.30 to NA)
7.29 [1] 
(5.78 to NA)
Extended 5-Year Analysis: 21 July 2019 Number Analyzed 172 participants 123 participants
14.65
(12.90 to 19.30)
9.23
(7.50 to 12.90)
[1]
NA = not estimable, could not be calculated due to too few events.
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 and during extended 5-year efficacy and safety follow-up analyses (Safety data cut-off: July 2019; up to 7 years, 6 months).
Adverse Event Reporting Description

1 participant was randomized in Placebo + Vem but did not receive any study treatment, 1 participant randomized in Cobi+ Vem but did not receive any study treatment, two participants were randomized in Placebo + Vem but received the Cobi+Vem.

All-cause Mortality is reported for the ITT population, SAEs and AEs are reported for the safety population. 1 participant died after 30 days from the last dose of treatment, after crossing over from the Placebo + Vem to the Cobi+Vem arm.

 
Arm/Group Title Cobimetinib + Vemurafenib Placebo + Vemurafenib
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Cobimetinib + Vemurafenib Placebo + Vemurafenib
Affected / at Risk (%) Affected / at Risk (%)
Total   160/247 (64.78%)      164/248 (66.13%)    
Hide Serious Adverse Events
Cobimetinib + Vemurafenib Placebo + Vemurafenib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   105/248 (42.34%)      71/245 (28.98%)    
Blood and lymphatic system disorders     
ANAEMIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
Cardiac disorders     
ACUTE CORONARY SYNDROME  1  1/248 (0.40%)  1 0/245 (0.00%)  0
ATRIAL FIBRILLATION  1  4/248 (1.61%)  8 1/245 (0.41%)  1
CARDIAC ARREST  1  1/248 (0.40%)  1 0/245 (0.00%)  0
CARDIAC FAILURE  1  1/248 (0.40%)  1 2/245 (0.82%)  2
CARDIAC TAMPONADE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
MYOCARDIAL INFARCTION  1  2/248 (0.81%)  2 0/245 (0.00%)  0
PERICARDIAL EFFUSION  1  0/248 (0.00%)  0 4/245 (1.63%)  4
SUPRAVENTRICULAR TACHYCARDIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
TACHYCARDIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
Endocrine disorders     
HYPERTHYROIDISM  1  1/248 (0.40%)  1 0/245 (0.00%)  0
Eye disorders     
CHORIORETINOPATHY  1  3/248 (1.21%)  5 0/245 (0.00%)  0
IRIDOCYCLITIS  1  0/248 (0.00%)  0 1/245 (0.41%)  1
RETINAL DETACHMENT  1  1/248 (0.40%)  1 0/245 (0.00%)  0
RETINAL HAEMORRHAGE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
SEROUS RETINAL DETACHMENT  1  2/248 (0.81%)  2 0/245 (0.00%)  0
UVEITIS  1  0/248 (0.00%)  0 1/245 (0.41%)  1
Gastrointestinal disorders     
ABDOMINAL PAIN  1  1/248 (0.40%)  1 0/245 (0.00%)  0
APHTHOUS ULCER  1  1/248 (0.40%)  1 0/245 (0.00%)  0
COLITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
CONSTIPATION  1  1/248 (0.40%)  1 0/245 (0.00%)  0
DIARRHOEA  1  3/248 (1.21%)  3 0/245 (0.00%)  0
DYSPHAGIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
GASTRIC ANTRAL VASCULAR ECTASIA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
GASTROINTESTINAL HAEMORRHAGE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
GASTROINTESTINAL PAIN  1  0/248 (0.00%)  0 1/245 (0.41%)  1
GASTROOESOPHAGEAL REFLUX DISEASE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
INGUINAL HERNIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
INTESTINAL OBSTRUCTION  1  0/248 (0.00%)  0 1/245 (0.41%)  1
INTESTINAL PERFORATION  1  1/248 (0.40%)  1 0/245 (0.00%)  0
MELAENA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
OBSTRUCTION GASTRIC  1  1/248 (0.40%)  1 0/245 (0.00%)  0
PANCREATITIS  1  1/248 (0.40%)  1 2/245 (0.82%)  2
PERIODONTAL DISEASE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
RECTAL POLYP  1  0/248 (0.00%)  0 1/245 (0.41%)  1
SMALL INTESTINAL OBSTRUCTION  1  3/248 (1.21%)  3 0/245 (0.00%)  0
VOMITING  1  2/248 (0.81%)  2 1/245 (0.41%)  1
General disorders     
ASTHENIA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
CHEST PAIN  1  1/248 (0.40%)  1 0/245 (0.00%)  0
DEATH  1  1/248 (0.40%)  1 1/245 (0.41%)  1
FATIGUE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
GAIT DISTURBANCE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
MALAISE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
PERIPHERAL SWELLING  1  0/248 (0.00%)  0 1/245 (0.41%)  1
PYREXIA  1  7/248 (2.82%)  9 3/245 (1.22%)  3
Hepatobiliary disorders     
CHOLECYSTITIS  1  0/248 (0.00%)  0 2/245 (0.82%)  2
DRUG-INDUCED LIVER INJURY  1  1/248 (0.40%)  1 0/245 (0.00%)  0
HEPATITIS ACUTE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
Immune system disorders     
HYPERSENSITIVITY  1  3/248 (1.21%)  3 0/245 (0.00%)  0
SARCOIDOSIS  1  1/248 (0.40%)  2 0/245 (0.00%)  0
Infections and infestations     
ABDOMINAL SEPSIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
ANAL ABSCESS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
ARTHRITIS BACTERIAL  1  0/248 (0.00%)  0 1/245 (0.41%)  1
CAMPYLOBACTER GASTROENTERITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
CELLULITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
CLOSTRIDIUM DIFFICILE COLITIS  1  1/248 (0.40%)  2 0/245 (0.00%)  0
CLOSTRIDIUM DIFFICILE INFECTION  1  1/248 (0.40%)  2 0/245 (0.00%)  0
DEVICE RELATED INFECTION  1  1/248 (0.40%)  1 0/245 (0.00%)  0
DIVERTICULITIS  1  1/248 (0.40%)  1 2/245 (0.82%)  2
ENTEROCOCCAL SEPSIS  1  1/248 (0.40%)  2 0/245 (0.00%)  0
ERYSIPELAS  1  1/248 (0.40%)  1 3/245 (1.22%)  4
GASTROENTERITIS  1  1/248 (0.40%)  1 1/245 (0.41%)  1
GASTROENTERITIS CLOSTRIDIAL  1  0/248 (0.00%)  0 1/245 (0.41%)  1
GASTROENTERITIS VIRAL  1  0/248 (0.00%)  0 1/245 (0.41%)  1
GASTROINTESTINAL BACTERIAL INFECTION  1  1/248 (0.40%)  1 0/245 (0.00%)  0
GENITOURINARY TRACT INFECTION  1  0/248 (0.00%)  0 1/245 (0.41%)  1
GROIN ABSCESS  1  1/248 (0.40%)  2 0/245 (0.00%)  0
INFECTION  1  1/248 (0.40%)  2 0/245 (0.00%)  0
PNEUMONIA  1  6/248 (2.42%)  6 3/245 (1.22%)  3
SEPSIS  1  1/248 (0.40%)  1 2/245 (0.82%)  2
SEPTIC SHOCK  1  1/248 (0.40%)  1 0/245 (0.00%)  0
TONSILLITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
TUBERCULOSIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
URINARY TRACT INFECTION  1  2/248 (0.81%)  2 1/245 (0.41%)  1
VULVAL CELLULITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
WOUND INFECTION  1  1/248 (0.40%)  1 0/245 (0.00%)  0
Injury, poisoning and procedural complications     
FACIAL BONES FRACTURE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
FALL  1  2/248 (0.81%)  4 0/245 (0.00%)  0
FEMORAL NECK FRACTURE  1  1/248 (0.40%)  1 1/245 (0.41%)  1
FRACTURE DISPLACEMENT  1  1/248 (0.40%)  1 0/245 (0.00%)  0
OVERDOSE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
RIB FRACTURE  1  1/248 (0.40%)  1 1/245 (0.41%)  1
SKIN LACERATION  1  1/248 (0.40%)  1 0/245 (0.00%)  0
THORACIC VERTEBRAL FRACTURE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
TRAUMATIC HAEMATOMA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
UPPER LIMB FRACTURE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  4/248 (1.61%)  4 2/245 (0.82%)  2
ASPARTATE AMINOTRANSFERASE INCREASED  1  3/248 (1.21%)  3 2/245 (0.82%)  2
BLOOD ALKALINE PHOSPHATASE INCREASED  1  1/248 (0.40%)  1 1/245 (0.41%)  1
BLOOD CREATINE PHOSPHOKINASE INCREASED  1  2/248 (0.81%)  2 0/245 (0.00%)  0
BLOOD CREATININE INCREASED  1  1/248 (0.40%)  1 0/245 (0.00%)  0
EJECTION FRACTION DECREASED  1  1/248 (0.40%)  1 1/245 (0.41%)  1
ELECTROCARDIOGRAM QT PROLONGED  1  0/248 (0.00%)  0 1/245 (0.41%)  1
ELECTROCARDIOGRAM T WAVE ABNORMAL  1  1/248 (0.40%)  1 0/245 (0.00%)  0
GAMMA-GLUTAMYLTRANSFERASE INCREASED  1  3/248 (1.21%)  3 1/245 (0.41%)  1
HAEMOGLOBIN DECREASED  1  1/248 (0.40%)  1 0/245 (0.00%)  0
LIPASE INCREASED  1  2/248 (0.81%)  2 0/245 (0.00%)  0
LIVER FUNCTION TEST INCREASED  1  1/248 (0.40%)  1 1/245 (0.41%)  1
Metabolism and nutrition disorders     
DEHYDRATION  1  6/248 (2.42%)  6 0/245 (0.00%)  0
DIABETES MELLITUS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
HYPERNATRAEMIA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
HYPOKALAEMIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
HYPONATRAEMIA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
TYPE 2 DIABETES MELLITUS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
BACK PAIN  1  0/248 (0.00%)  0 1/245 (0.41%)  1
BURSITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
MUSCULAR WEAKNESS  1  0/248 (0.00%)  0 1/245 (0.41%)  1
MUSCULOSKELETAL CHEST PAIN  1  1/248 (0.40%)  1 0/245 (0.00%)  0
MUSCULOSKELETAL PAIN  1  1/248 (0.40%)  1 0/245 (0.00%)  0
MYALGIA  1  1/248 (0.40%)  1 1/245 (0.41%)  1
PATHOLOGICAL FRACTURE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
POLYARTHRITIS  1  0/248 (0.00%)  0 1/245 (0.41%)  1
RHABDOMYOLYSIS  1  1/248 (0.40%)  1 1/245 (0.41%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
ACANTHOMA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
ADENOCARCINOMA OF COLON  1  1/248 (0.40%)  1 1/245 (0.41%)  1
BENIGN NEOPLASM  1  0/248 (0.00%)  0 1/245 (0.41%)  1
ENDOMETRIAL ADENOCARCINOMA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
GASTROINTESTINAL TRACT ADENOMA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
KAPOSI'S SARCOMA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
KERATOACANTHOMA  1  0/248 (0.00%)  0 4/245 (1.63%)  4
LUNG ADENOCARCINOMA  1  0/248 (0.00%)  0 2/245 (0.82%)  3
MALIGNANT MELANOMA IN SITU  1  0/248 (0.00%)  0 1/245 (0.41%)  1
MUCINOUS BREAST CARCINOMA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
PAPILLOMA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
SQUAMOUS CELL CARCINOMA OF SKIN  1  0/248 (0.00%)  0 1/245 (0.41%)  1
TRANSITIONAL CELL CARCINOMA  1  2/248 (0.81%)  2 0/245 (0.00%)  0
TUMOUR HAEMORRHAGE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
TUMOUR PAIN  1  0/248 (0.00%)  0 1/245 (0.41%)  1
Nervous system disorders     
CEREBRAL HAEMORRHAGE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
CEREBROVASCULAR ACCIDENT  1  2/248 (0.81%)  2 0/245 (0.00%)  0
COMA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
DIZZINESS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
DYSARTHRIA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
DYSGEUSIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
FACIAL PARALYSIS  1  2/248 (0.81%)  2 1/245 (0.41%)  1
FACIAL PARESIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
GENERALISED TONIC-CLONIC SEIZURE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
HAEMORRHAGIC STROKE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
HEADACHE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
HEMIPARESIS  1  2/248 (0.81%)  2 0/245 (0.00%)  0
HYDROCEPHALUS  1  0/248 (0.00%)  0 1/245 (0.41%)  1
ISCHAEMIC STROKE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
MYASTHENIA GRAVIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
PARAESTHESIA  1  0/248 (0.00%)  0 1/245 (0.41%)  1
POLYNEUROPATHY  1  1/248 (0.40%)  1 0/245 (0.00%)  0
SEIZURE  1  3/248 (1.21%)  3 0/245 (0.00%)  0
SUBARACHNOID HAEMORRHAGE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
SYNCOPE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
Psychiatric disorders     
MANIA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
Renal and urinary disorders     
ACUTE KIDNEY INJURY  1  3/248 (1.21%)  3 2/245 (0.82%)  3
DIABETIC NEPHROPATHY  1  1/248 (0.40%)  1 0/245 (0.00%)  0
RENAL COLIC  1  1/248 (0.40%)  1 0/245 (0.00%)  0
URETEROLITHIASIS  1  0/248 (0.00%)  0 1/245 (0.41%)  1
Reproductive system and breast disorders     
CERVICAL POLYP  1  0/248 (0.00%)  0 1/245 (0.41%)  1
Respiratory, thoracic and mediastinal disorders     
ATELECTASIS  1  0/248 (0.00%)  0 1/245 (0.41%)  1
DYSPNOEA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
INTERSTITIAL LUNG DISEASE  1  1/248 (0.40%)  1 0/245 (0.00%)  0
PLEURAL EFFUSION  1  0/248 (0.00%)  0 3/245 (1.22%)  3
PNEUMONITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
PULMONARY EMBOLISM  1  3/248 (1.21%)  3 1/245 (0.41%)  1
PULMONARY HAEMORRHAGE  1  0/248 (0.00%)  0 1/245 (0.41%)  1
Skin and subcutaneous tissue disorders     
DERMATITIS EXFOLIATIVE GENERALISED  1  0/248 (0.00%)  0 2/245 (0.82%)  2
DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS  1  1/248 (0.40%)  1 1/245 (0.41%)  1
ERYTHEMA MULTIFORME  1  0/248 (0.00%)  0 1/245 (0.41%)  1
ERYTHEMA NODOSUM  1  0/248 (0.00%)  0 1/245 (0.41%)  1
HYPERKERATOSIS  1  0/248 (0.00%)  0 1/245 (0.41%)  1
PANNICULITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
PHOTOSENSITIVITY REACTION  1  1/248 (0.40%)  1 0/245 (0.00%)  0
RASH  1  4/248 (1.61%)  4 2/245 (0.82%)  2
RASH GENERALISED  1  1/248 (0.40%)  1 0/245 (0.00%)  0
RASH MACULAR  1  1/248 (0.40%)  1 0/245 (0.00%)  0
RASH MACULO-PAPULAR  1  3/248 (1.21%)  3 2/245 (0.82%)  2
RASH MORBILLIFORM  1  1/248 (0.40%)  1 0/245 (0.00%)  0
URTICARIA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
Vascular disorders     
HYPERTENSION  1  1/248 (0.40%)  1 0/245 (0.00%)  0
HYPERTENSIVE CRISIS  1  2/248 (0.81%)  2 1/245 (0.41%)  1
SUBGALEAL HAEMATOMA  1  1/248 (0.40%)  1 0/245 (0.00%)  0
VASCULITIS  1  1/248 (0.40%)  1 0/245 (0.00%)  0
VENOUS THROMBOSIS LIMB  1  1/248 (0.40%)  1 0/245 (0.00%)  0
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.05%
Cobimetinib + Vemurafenib Placebo + Vemurafenib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   239/248 (96.37%)      236/245 (96.33%)    
Blood and lymphatic system disorders     
ANAEMIA  1  51/248 (20.56%)  76 21/245 (8.57%)  26
Eye disorders     
CHORIORETINOPATHY  1  30/248 (12.10%)  36 4/245 (1.63%)  9
VISION BLURRED  1  32/248 (12.90%)  37 8/245 (3.27%)  9
Gastrointestinal disorders     
ABDOMINAL PAIN  1  30/248 (12.10%)  37 20/245 (8.16%)  23
ABDOMINAL PAIN UPPER  1  15/248 (6.05%)  17 18/245 (7.35%)  21
CONSTIPATION  1  27/248 (10.89%)  37 29/245 (11.84%)  31
DIARRHOEA  1  151/248 (60.89%)  311 84/245 (34.29%)  162
DYSPEPSIA  1  19/248 (7.66%)  22 13/245 (5.31%)  15
NAUSEA  1  108/248 (43.55%)  184 67/245 (27.35%)  83
STOMATITIS  1  17/248 (6.85%)  27 3/245 (1.22%)  3
VOMITING  1  69/248 (27.82%)  108 33/245 (13.47%)  42
General disorders     
ASTHENIA  1  51/248 (20.56%)  96 43/245 (17.55%)  50
CHILLS  1  25/248 (10.08%)  28 14/245 (5.71%)  17
FATIGUE  1  93/248 (37.50%)  137 83/245 (33.88%)  99
OEDEMA PERIPHERAL  1  38/248 (15.32%)  49 28/245 (11.43%)  32
PYREXIA  1  77/248 (31.05%)  130 60/245 (24.49%)  77
Infections and infestations     
CONJUNCTIVITIS  1  18/248 (7.26%)  19 8/245 (3.27%)  10
FOLLICULITIS  1  19/248 (7.66%)  22 12/245 (4.90%)  15
NASOPHARYNGITIS  1  23/248 (9.27%)  29 18/245 (7.35%)  21
UPPER RESPIRATORY TRACT INFECTION  1  14/248 (5.65%)  18 11/245 (4.49%)  15
URINARY TRACT INFECTION  1  17/248 (6.85%)  25 11/245 (4.49%)  13
Injury, poisoning and procedural complications     
SUNBURN  1  37/248 (14.92%)  60 45/245 (18.37%)  68
Investigations     
ALANINE AMINOTRANSFERASE INCREASED  1  65/248 (26.21%)  94 44/245 (17.96%)  48
ASPARTATE AMINOTRANSFERASE INCREASED  1  64/248 (25.81%)  87 29/245 (11.84%)  30
BLOOD ALKALINE PHOSPHATASE INCREASED  1  46/248 (18.55%)  67 26/245 (10.61%)  30
BLOOD BILIRUBIN INCREASED  1  20/248 (8.06%)  29 17/245 (6.94%)  22
BLOOD CHOLESTEROL INCREASED  1  16/248 (6.45%)  19 10/245 (4.08%)  10
BLOOD CREATINE PHOSPHOKINASE INCREASED  1  90/248 (36.29%)  171 10/245 (4.08%)  13
BLOOD CREATININE INCREASED  1  45/248 (18.15%)  59 20/245 (8.16%)  25
BLOOD LACTATE DEHYDROGENASE INCREASED  1  15/248 (6.05%)  30 8/245 (3.27%)  8
EJECTION FRACTION DECREASED  1  31/248 (12.50%)  46 12/245 (4.90%)  13
ELECTROCARDIOGRAM QT PROLONGED  1  12/248 (4.84%)  15 13/245 (5.31%)  19
GAMMA-GLUTAMYLTRANSFERASE INCREASED  1  57/248 (22.98%)  82 45/245 (18.37%)  61
WEIGHT DECREASED  1  18/248 (7.26%)  20 14/245 (5.71%)  17
Metabolism and nutrition disorders     
DECREASED APPETITE  1  55/248 (22.18%)  75 50/245 (20.41%)  55
HYPONATRAEMIA  1  13/248 (5.24%)  19 3/245 (1.22%)  3
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  96/248 (38.71%)  172 105/245 (42.86%)  179
BACK PAIN  1  21/248 (8.47%)  30 15/245 (6.12%)  15
MUSCULOSKELETAL PAIN  1  17/248 (6.85%)  18 16/245 (6.53%)  19
MYALGIA  1  41/248 (16.53%)  53 33/245 (13.47%)  37
PAIN IN EXTREMITY  1  32/248 (12.90%)  51 40/245 (16.33%)  54
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
BASAL CELL CARCINOMA  1  16/248 (6.45%)  33 6/245 (2.45%)  6
KERATOACANTHOMA  1  5/248 (2.02%)  6 20/245 (8.16%)  26
MELANOCYTIC NAEVUS  1  5/248 (2.02%)  5 17/245 (6.94%)  26
SEBORRHOEIC KERATOSIS  1  15/248 (6.05%)  15 21/245 (8.57%)  24
SKIN PAPILLOMA  1  18/248 (7.26%)  26 30/245 (12.24%)  36
SQUAMOUS CELL CARCINOMA OF SKIN  1  10/248 (4.03%)  25 33/245 (13.47%)  66
Nervous system disorders     
DIZZINESS  1  18/248 (7.26%)  18 7/245 (2.86%)  8
DYSGEUSIA  1  27/248 (10.89%)  29 16/245 (6.53%)  17
HEADACHE  1  50/248 (20.16%)  76 41/245 (16.73%)  50
Psychiatric disorders     
ANXIETY  1  16/248 (6.45%)  18 11/245 (4.49%)  12
DEPRESSION  1  15/248 (6.05%)  17 11/245 (4.49%)  11
INSOMNIA  1  19/248 (7.66%)  24 27/245 (11.02%)  31
Respiratory, thoracic and mediastinal disorders     
COUGH  1  28/248 (11.29%)  36 32/245 (13.06%)  37
DYSPNOEA  1  19/248 (7.66%)  26 19/245 (7.76%)  23
OROPHARYNGEAL PAIN  1  19/248 (7.66%)  20 22/245 (8.98%)  28
Skin and subcutaneous tissue disorders     
ACTINIC KERATOSIS  1  13/248 (5.24%)  32 27/245 (11.02%)  31
ALOPECIA  1  42/248 (16.94%)  44 75/245 (30.61%)  78
DERMATITIS ACNEIFORM  1  37/248 (14.92%)  47 22/245 (8.98%)  26
DRY SKIN  1  37/248 (14.92%)  40 42/245 (17.14%)  46
ERYTHEMA  1  32/248 (12.90%)  56 36/245 (14.69%)  57
HYPERKERATOSIS  1  31/248 (12.50%)  39 74/245 (30.20%)  130
KERATOSIS PILARIS  1  13/248 (5.24%)  14 26/245 (10.61%)  30
PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME  1  18/248 (7.26%)  23 9/245 (3.67%)  10
PHOTOSENSITIVITY REACTION  1  86/248 (34.68%)  119 48/245 (19.59%)  58
PRURITUS  1  51/248 (20.56%)  85 48/245 (19.59%)  54
RASH  1  101/248 (40.73%)  158 97/245 (39.59%)  121
RASH MACULO-PAPULAR  1  37/248 (14.92%)  61 37/245 (15.10%)  47
SOLAR DERMATITIS  1  18/248 (7.26%)  34 14/245 (5.71%)  23
Vascular disorders     
HYPERTENSION  1  50/248 (20.16%)  60 30/245 (12.24%)  33
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01689519    
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: September 16, 2020