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Trial record 70 of 519 for:    melanoma phase III

A Study of Vemurafenib (RO5185426) in Comparison With Dacarbazine in Previously Untreated Patients With Metastatic Melanoma (BRIM 3)

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ClinicalTrials.gov Identifier: NCT01006980
Recruitment Status : Completed
First Posted : November 3, 2009
Results First Posted : November 16, 2011
Last Update Posted : September 28, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Melanoma
Interventions Drug: Vemurafenib
Drug: Dacarbazine
Enrollment 675
Recruitment Details  
Pre-assignment Details 675 participants were randomized, 337 to vemurafenib and 338 to dacarbazine. One participant randomized to dacarbazine was treated in error with vemurafenib throughout the study and is included in the Vemurafenib arm in the table below and for exposure and safety analyses and is included in the dacarbazine arm for efficacy analyses.
Arm/Group Title Vemurafenib Dacarbazine
Hide Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
Period Title: Vemurafenib and Dacarbazine
Started 337 338
Treated 336 293
Completed 0 0
Not Completed 337 338
Reason Not Completed
Randomized but Not Treated             1             45
Adverse Event             25             5
Death             13             12
Progression             257             218
Withdrawal of Consent             4             6
Refuse Treatment             9             6
Protocol Violation             2             3
Reason Not Specified             26             43
Period Title: Crossover: Dacarbazine to Vemurafenib
Started 0 84 [1]
Completed 0 0
Not Completed 0 84
Reason Not Completed
Adverse Event             0             4
Death             0             4
Progression             0             65
Withdrawal of Consent             0             1
Reason Not Specified             0             10
[1]
Participants who crossed over from dacarbazine to vemurafenib treatment.
Arm/Group Title Vemurafenib Dacarbazine Total
Hide Arm/Group Description Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg). Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length). Total of all reporting groups
Overall Number of Baseline Participants 337 338 675
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 337 participants 338 participants 675 participants
< 65 years 244 270 514
>=65 years 93 68 161
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 337 participants 338 participants 675 participants
Female
137
  40.7%
157
  46.4%
294
  43.6%
Male
200
  59.3%
181
  53.6%
381
  56.4%
1.Primary Outcome
Title Overall Survival
Hide Description An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.
Time Frame From randomization (initiated January 2010) to December 30 2010. Median follow-up time in the vemurafenib group was 3.75 months (range 0.3 to 10.8) and in the dacarbazine group was 2.33 months (range <0.1 to 10.3).
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Hide Analysis Population Description
The intent-to-treat (ITT) population was defined as all randomized participants, whether or not study treatment was received. The ITT population was analyzed according to the treatment assigned at randomization. Overall survival was assessed on participants randomized at least 15 days prior to the clinical cutoff date of December 30, 2010.
Arm/Group Title Vemurafenib Dacarbazine
Hide Arm/Group Description:
Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
Overall Number of Participants Analyzed 336 336
Measure Type: Number
Unit of Measure: participants
Participants with events 43 75
Participants without events 293 261
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vemurafenib, Dacarbazine
Comments The trial had a power of 80% to detect a hazard ratio of 0.65 for overall survival with an alpha level of 0.045 (an increase in median survival from 8 months for dacarbazine to 12.3 months for vemurafenib), one interim analysis for overall survival at 50% information.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.26 to 0.55
Estimation Comments The hazard ratio for death for vemurafenib relative to dacarbazine and the associated 95% confidence interval were computed using an unstratified Cox regression model.
2.Primary Outcome
Title Progression-free Survival
Hide Description A progression-free survival (PFS) event was defined as disease progression or death due to any cause. Tumor response (progression) was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria using computed tomography (CT) scans or magnetic resonance imaging (MRI).
Time Frame From randomization (initiated January 2010) to December 30 2010.
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Hide Analysis Population Description
The analysis population for PFS consisted of all ITT participants randomized by October 27, 2010 (at least 9 weeks prior to the clinical cutoff date of December 30, 2010). The 9-week interval was chosen to allow time for participants to have had their first scheduled post baseline tumor assessment CT scan.
Arm/Group Title Vemurafenib Dacarbazine
Hide Arm/Group Description:
Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
Overall Number of Participants Analyzed 275 274
Measure Type: Number
Unit of Measure: participants
Participants with events 104 182
Participants without events 171 92
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vemurafenib, Dacarbazine
Comments The trial had a power of 90% to detect a hazard ratio of 0.55 for progression-free survival with an alpha level of 0.005 (an increase in median survival from 2.5 months for dacarbazine to 4.5 months for vemurafenib).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.26
Confidence Interval (2-Sided) 95%
0.20 to 0.33
Estimation Comments Hazard ratios for treatment with vemurafenib, as compared with dacarbazine, were estimated with the use of unstratified Cox regression.
3.Secondary Outcome
Title Participants With a Best Overall Response (BOR) of Complete Response or Partial Response
Hide Description BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Participants who never received study treatment and treated participants without any post-baseline tumor assessments were considered as non-responders. CR: Disappearance of all target lesions, all non-target lesions and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion and no new lesion.
Time Frame From randomization (initiated January 2010) until December 30, 2010
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Hide Analysis Population Description
The analysis population consisted of all ITT participants randomized by September 22, 2010 (at least 14 weeks prior to the clinical cutoff date of December 30, 2010). The 14-week interval was chosen as it was the minimum time needed to observe a confirmed overall response according to protocol-specified schedule for the first two tumor assessments.
Arm/Group Title Vemurafenib Dacarbazine
Hide Arm/Group Description:
Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
Overall Number of Participants Analyzed 219 220
Measure Type: Number
Unit of Measure: participants
Responders 106 12
Non-responders 113 208
4.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was defined as the time between the date of the earliest qualifying response and the date of disease progression or death due to any cause. Duration of response was calculated only for participants who had a best overall response of Complete Response or Partial Response and was estimated using the Kaplan–Meier method.
Time Frame From randomization (initiated in January 2010) until December 30, 2010.
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Hide Analysis Population Description
The analysis population included all participants randomized by September 22, 2010 and with a best overall confirmed response of complete response or partial response.
Arm/Group Title Vemurafenib Dacarbazine
Hide Arm/Group Description:
Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
Overall Number of Participants Analyzed 106 12
Median (95% Confidence Interval)
Unit of Measure: months
5.49
(3.98 to 5.72)
NA [1] 
(4.60 to NA)
[1]
Median duration of response was not reached as only 2 of the 12 participants with a qualifying response had subsequent disease progression or death due to any cause at the time of the analysis.
5.Secondary Outcome
Title Time to Confirmed Response
Hide Description Time to response was defined as the time from randomization to confirmed response (complete response or partial response).
Time Frame From randomization (initiated January 2010) until December 30, 2010.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants randomized by September 22, 2010 and with a best overall confirmed response of complete response or partial response.
Arm/Group Title Vemurafenib Dacarbazine
Hide Arm/Group Description:
Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
Overall Number of Participants Analyzed 106 12
Median (Full Range)
Unit of Measure: months
1.45
(1.0 to 5.5)
2.72
(1.6 to 5.8)
6.Secondary Outcome
Title Time to Treatment Failure
Hide Description Treatment failure was defined as a secondary endpoint in the protocol, defined as death, disease progression or premature withdrawal of study treatment. This endpoint was not included in the Statistical analysis plan; therefore no analyses of time to treatment failure were performed.
Time Frame approximately 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Vemurafenib Dacarbazine
Hide Arm/Group Description:
Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description The intensity of AEs was graded according to the NCI Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death). A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution, for example is life-threatening, requires hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or requires intervention to prevent one or other of the outcomes listed above.
Time Frame From randomization (initiated January 2010) until December 30, 2010.
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Hide Analysis Population Description
The safety population was defined as all treated participants who had at least one on-study assessment. The safety population was analyzed according to the treatment received.
Arm/Group Title Vemurafenib Dacarbazine
Hide Arm/Group Description:
Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).
Overall Number of Participants Analyzed 336 282
Measure Type: Number
Unit of Measure: participants
Any adverse event 326 253
Serious adverse event 110 45
8.Secondary Outcome
Title Pre and Post-dose Plasma Vemurafenib Concentration by Study Day
Hide Description The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.
Time Frame Plasma samples were collected before the morning dose (troughs) and 2-4 hours after the morning dose at the beginning of each cycle (Days 1, 22, 43, 64, 106, 148 and 190).
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Hide Analysis Population Description
The pharmacokinetic (PK) analysis population included all participants who received vemurafenib and provided valid PK assessments. The PK population at specific time points varied depending on the availability of confirmed dosing and PK assessment times. "n" indicates the number of participants with available PK data at each time point.
Arm/Group Title Vemurafenib
Hide Arm/Group Description:
Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).
Overall Number of Participants Analyzed 260
Mean (Standard Deviation)
Unit of Measure: μg/mL
Pre-Dose Day 1 (n = 260) 0  (0)
Post-Dose Day 1 (n = 255) 4.3  (4.35)
Pre-Dose Day 22 (n = 204) 53.0  (26.66)
Post-Dose Day 22 (n = 221) 54.0  (25.67)
Pre-Dose Day 43 (n = 166) 54.4  (24.13)
Post-Dose Day 43 (n = 170) 54.4  (23.28)
Pre-Dose Day 64 (n = 141) 57.4  (23.79)
Post-Dose Day 64 (n = 138) 57.7  (22.29)
Pre-Dose Day 106 (n = 77) 55.0  (17.62)
Post-Dose Day 106 (n = 75) 56.3  (20.36)
Pre-Dose Day 148 (n = 38) 51.8  (24.13)
Post-Dose Day 148 (n = 39) 53.3  (21.55)
Pre-Dose Day 190 (n = 9) 53.6  (12.6)
Post-Dose Day 190 (n = 9) 50.5  (20.16)
Time Frame Baseline through the end of study (maximum exposure: 57.07 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vemurafenib Dacarbazine Vemurafenib After Crossover
Hide Arm/Group Description

Adverse events reported for this group include those occurring in participants receiving vemurafenib starting at their baseline visit.

Participants received continuous oral doses of vemurafenib (RO5185426) 960 mg twice a day. Participants took four 240 mg tablets in the morning and four 240 mg tablets in the evening (960 mg twice a day for a total daily dose of 1920 mg).

Adverse events reported for this group include those occurring in participants receiving dacarbazine starting at their baseline visit until study discontinuation or treatment switch.

Dacarbazine was administered intravenously 1000 mg/m˄2 up to 60 minutes on Day 1 of every 3 weeks (3 weeks was one cycle length).

Adverse events reported for this group include those occurring following switch to vemurafenib in those participants who switched from dacarbazine to vemurafenib during the study.
All-Cause Mortality
Vemurafenib Dacarbazine Vemurafenib After Crossover
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vemurafenib Dacarbazine Vemurafenib After Crossover
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   165/336 (49.11%)   52/293 (17.75%)   44/84 (52.38%) 
Blood and lymphatic system disorders       
Anaemia  1  0/336 (0.00%)  0/293 (0.00%)  2/84 (2.38%) 
Bone marrow failure  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Lymphadenitis  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Neutropenia  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Thrombocytopenia  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Cardiac disorders       
Acute myocardial infarction  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Atrial fibrillation  1  3/336 (0.89%)  0/293 (0.00%)  0/84 (0.00%) 
Atrial tachycardia  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Cardiac arrest  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Cardiac failure  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Cardiac failure congestive  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Cardiac tamponade  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Cardiopulmonary failure  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Coronary artery disease  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Myocardial infarction  1  2/336 (0.60%)  0/293 (0.00%)  0/84 (0.00%) 
Pericardial effusion  1  1/336 (0.30%)  0/293 (0.00%)  1/84 (1.19%) 
Pericarditis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Eye disorders       
Diplopia  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Orbital oedema  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Uveitis  1  3/336 (0.89%)  0/293 (0.00%)  0/84 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  2/336 (0.60%)  1/293 (0.34%)  0/84 (0.00%) 
Abdominal pain lower  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Abdominal pain upper  1  1/336 (0.30%)  0/293 (0.00%)  1/84 (1.19%) 
Constipation  1  1/336 (0.30%)  0/293 (0.00%)  1/84 (1.19%) 
Diarrhoea haemorrhagic  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Gastric ulcer  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Gastrointestinal haemorrhage  1  2/336 (0.60%)  0/293 (0.00%)  0/84 (0.00%) 
Gastrointestinal ulcer  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Gastrooesophageal reflux disease  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Intussusception  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Large intestinal obstruction  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Pancreatitis  1  2/336 (0.60%)  1/293 (0.34%)  0/84 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Vomiting  1  1/336 (0.30%)  0/293 (0.00%)  1/84 (1.19%) 
General disorders       
Asthenia  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Chest pain  1  3/336 (0.89%)  0/293 (0.00%)  0/84 (0.00%) 
Device occlusion  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Fatigue  1  2/336 (0.60%)  1/293 (0.34%)  1/84 (1.19%) 
Gait disturbance  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
General physical health deterioration  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Malaise  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Oedema peripheral  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Pyrexia  1  5/336 (1.49%)  4/293 (1.37%)  3/84 (3.57%) 
Hepatobiliary disorders       
Cholecystitis  1  1/336 (0.30%)  0/293 (0.00%)  1/84 (1.19%) 
Hepatitis acute  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Immune system disorders       
Hypersensitivity  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Infections and infestations       
Anal abscess  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Bronchitis  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Cellulitis  1  1/336 (0.30%)  1/293 (0.34%)  1/84 (1.19%) 
Diverticulitis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Encephalitis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Erysipelas  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Gastroenteritis  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Herpes virus infection  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Intervertebral discitis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Lower respiratory tract infection  1  1/336 (0.30%)  0/293 (0.00%)  1/84 (1.19%) 
Lung infection  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Osteomyelitis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Pneumonia  1  5/336 (1.49%)  2/293 (0.68%)  2/84 (2.38%) 
Sepsis  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Skin infection  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Soft tissue infection  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Upper respiratory tract infection  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Urinary tract infection  1  1/336 (0.30%)  0/293 (0.00%)  1/84 (1.19%) 
Viral infection  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Wound infection staphylococcal  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Femoral neck fracture  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Hip fracture  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Multiple injuries  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  1/336 (0.30%)  1/293 (0.34%)  1/84 (1.19%) 
Aspartate aminotransferase increased  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Blood alkaline phosphatase increased  1  2/336 (0.60%)  0/293 (0.00%)  0/84 (0.00%) 
Blood bilirubin increased  1  2/336 (0.60%)  0/293 (0.00%)  0/84 (0.00%) 
Gamma−glutamyltransferase increased  1  2/336 (0.60%)  0/293 (0.00%)  2/84 (2.38%) 
International normalised ratio decreased  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Liver function test abnormal  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Neutrophil count decreased  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Metabolism and nutrition disorders       
Dehydration  1  2/336 (0.60%)  0/293 (0.00%)  0/84 (0.00%) 
Diabetes mellitus  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Failure to thrive  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Hypercalcaemia  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Hyperkalaemia  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Hyperuricaemia  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Hypoglycaemia  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Hyponatraemia  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  3/336 (0.89%)  2/293 (0.68%)  0/84 (0.00%) 
Bone pain  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Groin pain  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Hypercreatinaemia  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Intervertebral disc protrusion  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Joint effusion  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Musculoskeletal chest pain  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Musculoskeletal pain  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Myalgia  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Neck pain  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Pain in extremity  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Pathological fracture  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Spinal pain  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  10/336 (2.98%)  2/293 (0.68%)  3/84 (3.57%) 
Bowen’s disease  1  3/336 (0.89%)  0/293 (0.00%)  0/84 (0.00%) 
Intracranial tumour haemorrhage  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Keratoacanthoma  1  36/336 (10.71%)  3/293 (1.02%)  6/84 (7.14%) 
Malignant melanoma  1  7/336 (2.08%)  0/293 (0.00%)  1/84 (1.19%) 
Malignant melanoma in situ  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Skin papilloma  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Squamous cell carcinoma of skin  1  66/336 (19.64%)  2/293 (0.68%)  12/84 (14.29%) 
Tonsil cancer  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Nervous system disorders       
Aphasia  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Cerebrovascular accident  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Epilepsy  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Headache  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Intraventricular haemorrhage  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Loss of consciousness  1  2/336 (0.60%)  0/293 (0.00%)  0/84 (0.00%) 
Peripheral sensorimotor neuropathy  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Sciatica  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Seizure  1  2/336 (0.60%)  0/293 (0.00%)  1/84 (1.19%) 
Sensorimotor disorder  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Syncope  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
VIIth nerve paralysis  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Psychiatric disorders       
Completed suicide  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Confusional state  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  3/336 (0.89%)  1/293 (0.34%)  1/84 (1.19%) 
Haemorrhage urinary tract  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Renal failure  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Renal impairment  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Reproductive system and breast disorders       
Cervical dysplasia  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Dyspnoea  1  3/336 (0.89%)  2/293 (0.68%)  0/84 (0.00%) 
Epistaxis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Haemoptysis  1  1/336 (0.30%)  1/293 (0.34%)  0/84 (0.00%) 
Pleural effusion  1  3/336 (0.89%)  0/293 (0.00%)  0/84 (0.00%) 
Pleuritic pain  1  2/336 (0.60%)  0/293 (0.00%)  0/84 (0.00%) 
Pneumothorax  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Pulmonary embolism  1  4/336 (1.19%)  2/293 (0.68%)  0/84 (0.00%) 
Skin and subcutaneous tissue disorders       
Photosensitivity reaction  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Rash  1  3/336 (0.89%)  0/293 (0.00%)  0/84 (0.00%) 
Skin lesion  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Stevens-Johnson syndrome  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Toxic epidermal necrolysis  1  0/336 (0.00%)  0/293 (0.00%)  1/84 (1.19%) 
Vascular disorders       
Deep vein thrombosis  1  0/336 (0.00%)  1/293 (0.34%)  1/84 (1.19%) 
Haematoma  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Hypertension  1  1/336 (0.30%)  0/293 (0.00%)  1/84 (1.19%) 
Hypertensive crisis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Shock  1  0/336 (0.00%)  1/293 (0.34%)  0/84 (0.00%) 
Subclavian vein thrombosis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Thrombosis  1  0/336 (0.00%)  2/293 (0.68%)  0/84 (0.00%) 
Vasculitis  1  1/336 (0.30%)  0/293 (0.00%)  0/84 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vemurafenib Dacarbazine Vemurafenib After Crossover
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   333/336 (99.11%)   247/293 (84.30%)   83/84 (98.81%) 
Blood and lymphatic system disorders       
Anaemia  1  32/336 (9.52%)  22/293 (7.51%)  13/84 (15.48%) 
Neutropenia  1  1/336 (0.30%)  34/293 (11.60%)  0/84 (0.00%) 
Thrombocytopenia  1  5/336 (1.49%)  20/293 (6.83%)  1/84 (1.19%) 
Gastrointestinal disorders       
Abdominal Distension  1  18/336 (5.36%)  5/293 (1.71%)  2/84 (2.38%) 
Abdominal Pain  1  35/336 (10.42%)  12/293 (4.10%)  3/84 (3.57%) 
Abdominal Pain Upper  1  37/336 (11.01%)  8/293 (2.73%)  5/84 (5.95%) 
Constipation  1  52/336 (15.48%)  72/293 (24.57%)  8/84 (9.52%) 
Diarrhoea  1  124/336 (36.90%)  36/293 (12.29%)  24/84 (28.57%) 
Dyspepsia  1  20/336 (5.95%)  2/293 (0.68%)  2/84 (2.38%) 
Nausea  1  132/336 (39.29%)  128/293 (43.69%)  33/84 (39.29%) 
Vomiting  1  73/336 (21.73%)  77/293 (26.28%)  20/84 (23.81%) 
General disorders       
Asthenia  1  50/336 (14.88%)  29/293 (9.90%)  7/84 (8.33%) 
Chest Pain  1  26/336 (7.74%)  5/293 (1.71%)  4/84 (4.76%) 
Chills  1  23/336 (6.85%)  3/293 (1.02%)  2/84 (2.38%) 
Fatigue  1  158/336 (47.02%)  101/293 (34.47%)  32/84 (38.10%) 
Influenza Like Illness  1  29/336 (8.63%)  5/293 (1.71%)  3/84 (3.57%) 
Oedema Peripheral  1  49/336 (14.58%)  15/293 (5.12%)  8/84 (9.52%) 
Pain  1  30/336 (8.93%)  14/293 (4.78%)  2/84 (2.38%) 
Peripheral Swelling  1  26/336 (7.74%)  0/293 (0.00%)  5/84 (5.95%) 
Pyrexia  1  71/336 (21.13%)  26/293 (8.87%)  18/84 (21.43%) 
Infections and infestations       
Conjunctivitis  1  20/336 (5.95%)  1/293 (0.34%)  2/84 (2.38%) 
Folliculitis  1  28/336 (8.33%)  3/293 (1.02%)  2/84 (2.38%) 
Influenza  1  18/336 (5.36%)  4/293 (1.37%)  3/84 (3.57%) 
Nasopharyngitis  1  36/336 (10.71%)  10/293 (3.41%)  4/84 (4.76%) 
Upper Respiratory Tract Infection  1  19/336 (5.65%)  5/293 (1.71%)  4/84 (4.76%) 
Lower respiratory tract infection  1  8/336 (2.38%)  2/293 (0.68%)  6/84 (7.14%) 
Urinary tract infection  1  9/336 (2.68%)  9/293 (3.07%)  5/84 (5.95%) 
Injury, poisoning and procedural complications       
Sunburn  1  57/336 (16.96%)  0/293 (0.00%)  15/84 (17.86%) 
Investigations       
Alanine Aminotransferase Increased  1  28/336 (8.33%)  4/293 (1.37%)  6/84 (7.14%) 
Aspartate Aminotransferase Increased  1  25/336 (7.44%)  3/293 (1.02%)  8/84 (9.52%) 
Blood Alkaline Phosphatase Increased  1  33/336 (9.82%)  0/293 (0.00%)  9/84 (10.71%) 
Blood Bilirubin Increased  1  31/336 (9.23%)  1/293 (0.34%)  2/84 (2.38%) 
Blood Creatinine Increased  1  28/336 (8.33%)  1/293 (0.34%)  7/84 (8.33%) 
Gamma−Glutamyltransferase Increased  1  24/336 (7.14%)  4/293 (1.37%)  7/84 (8.33%) 
Weight Decreased  1  32/336 (9.52%)  8/293 (2.73%)  4/84 (4.76%) 
Metabolism and nutrition disorders       
Decreased Appetite  1  76/336 (22.62%)  24/293 (8.19%)  20/84 (23.81%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  189/336 (56.25%)  9/293 (3.07%)  48/84 (57.14%) 
Back Pain  1  53/336 (15.77%)  20/293 (6.83%)  11/84 (13.10%) 
Musculoskeletal Pain  1  44/336 (13.10%)  11/293 (3.75%)  12/84 (14.29%) 
Myalgia  1  50/336 (14.88%)  5/293 (1.71%)  15/84 (17.86%) 
Pain In Extremity  1  76/336 (22.62%)  18/293 (6.14%)  14/84 (16.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Melanocytic Naevus  1  39/336 (11.61%)  3/293 (1.02%)  9/84 (10.71%) 
Seborrhoeic Keratosis  1  46/336 (13.69%)  2/293 (0.68%)  8/84 (9.52%) 
Skin Papilloma  1  96/336 (28.57%)  1/293 (0.34%)  17/84 (20.24%) 
Nervous system disorders       
Dizziness  1  41/336 (12.20%)  14/293 (4.78%)  3/84 (3.57%) 
Dysgeusia  1  55/336 (16.37%)  10/293 (3.41%)  9/84 (10.71%) 
Headache  1  113/336 (33.63%)  29/293 (9.90%)  23/84 (27.38%) 
Hyperaesthesia  1  17/336 (5.06%)  1/293 (0.34%)  0/84 (0.00%) 
Paraesthesia  1  30/336 (8.93%)  16/293 (5.46%)  6/84 (7.14%) 
Psychiatric disorders       
Depression  1  21/336 (6.25%)  7/293 (2.39%)  3/84 (3.57%) 
Insomnia  1  37/336 (11.01%)  16/293 (5.46%)  7/84 (8.33%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  52/336 (15.48%)  24/293 (8.19%)  6/84 (7.14%) 
Dyspnoea  1  33/336 (9.82%)  24/293 (8.19%)  8/84 (9.52%) 
Oropharyngeal Pain  1  27/336 (8.04%)  5/293 (1.71%)  3/84 (3.57%) 
Skin and subcutaneous tissue disorders       
Actinic Keratosis  1  44/336 (13.10%)  12/293 (4.10%)  13/84 (15.48%) 
Alopecia  1  162/336 (48.21%)  7/293 (2.39%)  25/84 (29.76%) 
Dermal Cyst  1  26/336 (7.74%)  1/293 (0.34%)  3/84 (3.57%) 
Dermatitis Acneiform  1  18/336 (5.36%)  1/293 (0.34%)  4/84 (4.76%) 
Dry Skin  1  80/336 (23.81%)  2/293 (0.68%)  16/84 (19.05%) 
Erythema  1  61/336 (18.15%)  4/293 (1.37%)  12/84 (14.29%) 
Hyperkeratosis  1  99/336 (29.46%)  1/293 (0.34%)  15/84 (17.86%) 
Keratosis Pilaris  1  32/336 (9.52%)  1/293 (0.34%)  7/84 (8.33%) 
Palmar−Plantar Erythrodysaesthesia Syndrome  1  34/336 (10.12%)  2/293 (0.68%)  11/84 (13.10%) 
Photosensitivity Reaction  1  136/336 (40.48%)  13/293 (4.44%)  26/84 (30.95%) 
Pruritus  1  86/336 (25.60%)  5/293 (1.71%)  14/84 (16.67%) 
Rash  1  143/336 (42.56%)  6/293 (2.05%)  28/84 (33.33%) 
Rash Maculo−Papular  1  34/336 (10.12%)  1/293 (0.34%)  10/84 (11.90%) 
Skin Exfoliation  1  18/336 (5.36%)  0/293 (0.00%)  2/84 (2.38%) 
Skin Lesion  1  40/336 (11.90%)  4/293 (1.37%)  4/84 (4.76%) 
Acne  1  15/336 (4.46%)  0/293 (0.00%)  5/84 (5.95%) 
Rash erythematous  1  9/336 (2.68%)  0/293 (0.00%)  5/84 (5.95%) 
Vascular disorders       
Flushing  1  17/336 (5.06%)  6/293 (2.05%)  2/84 (2.38%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
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: Hoffman-LaRoche
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: NCT01006980     History of Changes
Other Study ID Numbers: NO25026
2009-012293-12
First Submitted: October 30, 2009
First Posted: November 3, 2009
Results First Submitted: July 29, 2011
Results First Posted: November 16, 2011
Last Update Posted: September 28, 2016