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A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases

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ClinicalTrials.gov Identifier: NCT01378975
Recruitment Status : Completed
First Posted : June 23, 2011
Results First Posted : August 1, 2016
Last Update Posted : August 1, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Melanoma
Intervention Drug: Vemurafenib
Enrollment 146
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor. Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Period Title: Overall Study
Started 90 56
Completed 4 6
Not Completed 86 50
Reason Not Completed
Death             77             46
Investigator Request             1             0
Lost to Follow-up             4             1
Withdrew Consent             4             3
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants Total
Hide Arm/Group Description Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor. Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor. Total of all reporting groups
Overall Number of Baseline Participants 90 56 146
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population included all participants who were enrolled in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 90 participants 56 participants 146 participants
55.7  (12.73) 52.7  (13.85) 54.5  (13.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 56 participants 146 participants
Female
34
  37.8%
22
  39.3%
56
  38.4%
Male
56
  62.2%
34
  60.7%
90
  61.6%
1.Primary Outcome
Title Best Overall Response Rate (BORR) Within Brain of Previously Untreated Participants (Assessed by Independent Review Committee [IRC] Using Modified Response Evaluation Criteria in Solid Tumors [RECIST])
Hide Description BORR assessed by IRC is defined as percentage of participants who were responders [with best overall response (BOR) documented as confirmed complete response (CR) or partial response (PR)]. The RECIST v1.1 criteria modified for independent review of body and brain lesions was based on current radiology practices. The modifications to RECIST v1.1 included allowing target lesions in the brain to be >=5 mm by contrast-enhanced magnetic resonance imaging scan (in traditional RECIST v1.1 this is >=10 mm), allowing up to 5 target lesions in the brain (in traditional RECIST v1.1 only 2 target lesions), and examining the lesions within the brain and outside the brain separately for analytical purposes. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm), PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat (ITT) population included all participants who were enrolled in the study.
Arm/Group Title Cohort 1: Previously Untreated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.8
(10.5 to 27.3)
2.Secondary Outcome
Title Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated or Untreated Brain Metastases as Assessed by the IRC Using RECIST v1.1
Hide Description Percentage of participants who were responders with BOR documented as confirmed CR or PR, stable disease (SD), progressive disease (PD). CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90 56
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response 2.2 0.0
Partial Response 15.6 17.9
Stable Disease 43.3 41.1
Progressive Disease 32.2 33.9
Unevaluable 6.7 7.1
3.Secondary Outcome
Title Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1
Hide Description BORR within brain assessed by IRC is defined as percentage of participants who were responders (with BOR documented as confirmed CR or PR). According to RECIST v1.1 criteria modified for brain metastases, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study.
Arm/Group Title Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17.9
(8.9 to 30.4)
4.Secondary Outcome
Title Best Overall Response Rate Outside the Brain (Assessed by IRC)
Hide Description BORR outside of brain assessed by IRC is defined as percentage of participants who were responders (with BOR documented as confirmed CR or PR). According to RECIST v1.1 criteria modified for brain metastases, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study. Here, number participants analyzed is the total number of participants who had measurable disease outside brain at baseline.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 79 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
32.9
(22.7 to 44.4)
22.5
(10.8 to 38.5)
5.Secondary Outcome
Title Duration of Response (DOR) (Assessed by Investigator and IRC)
Hide Description Duration of response was defined as the time interval between the date of the earliest qualifying response and the earliest date of PD or death from any cause. For participants who were alive without progression following the qualifying response, DOR were censored on the date of last available tumor assessment on or before the data cutoff date.
Time Frame Date of the earliest qualifying response until the earliest date of PD or death from any cause (approximately up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study. Here, 'n' indicates number of participants who were responders within brain or outside brain assessed by investigator or IRC.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90 56
Median (Full Range)
Unit of Measure: months
Investigator: DOR (Within Brain) (n=26, 13)
4.67
(2.66 to 24.21)
6.64
(1.87 to 21.98)
Investigator: DOR (Outside Brain) (n=25, 11)
5.55
(1.84 to 25.63)
10.74
(1.84 to 23.10)
IRC: DOR (Within Brain) (n=16, 10)
4.60
(2.66 to 29.90)
6.64
(0.95 to 18.40)
IRC: DOR (Outside Brain) (n=26, 9)
7.72
(1.84 to 21.55)
11.07
(1.84 to 23.10)
6.Secondary Outcome
Title Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator)
Hide Description Progression-free survival was defined as the time between enrollment on Day 1 and the date of first radiographically documented progressive disease (within or outside the brain), clinical progressive disease, as assessed by the investigator or death whichever occurred first.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90 56
Median (Full Range)
Unit of Measure: months
3.65
(0.30 to 33.35)
3.71
(0.26 to 27.37)
7.Secondary Outcome
Title Progression-Free Survival (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator )
Hide Description Progression-free survival was defined as the time between enrollment on Day 1 and the date of first radiographically documented progressive disease (within brain), clinical progressive disease, as assessed by the investigator or death whichever occurred first.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90 56
Median (Full Range)
Unit of Measure: months
3.68
(0.36 to 33.35)
4.04
(0.26 to 27.37)
8.Secondary Outcome
Title Time to Development of New Brain Metastases in Responders
Hide Description Time to development of new lesions within the brain was defined as the interval between the date of first treatment and the earliest date of documentation of new brain lesions. Participants who were known to be free of new lesions were censored on the date of last tumor assessment.
Time Frame Date of first treatment and the earliest date of documentation of new brain lesions (approximately up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study. Here, number of participants analyzed is the participants who were responders.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 26 13
Median (Full Range)
Unit of Measure: months
14.92
(3.48 to 33.35)
14.52
(2.79 to 27.37)
9.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as time between enrollment on Day 1 and date of death, irrespective of the cause of death. Participants for whom no death was captured on the clinical database were censored at the latest date they were known to be alive prior to or on the cutoff date.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90 56
Median (Full Range)
Unit of Measure: months
8.87
(0.59 to 34.53)
9.63
(0.66 to 34.30)
10.Secondary Outcome
Title Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator)
Hide Description Percentage of participants who were responders with BOR documented as confirmed CR or PR, stable disease (SD), progressive disease (PD). CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study. Here, ‘n’ indicates the number participants who were evaluable for within brain assessment and who had measurable disease outside brain at baseline for outside brain assessment.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90 56
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response (Within Brain) (n=90, 56) 2.2 0.0
Partial Response (Within Brain) (n=90, 56) 26.7 23.2
Stable Disease (Within Brain) (n=90, 56) 40.0 53.6
Progressive Disease (Within Brain) (n=90, 56) 27.8 19.6
Unevaluable (Within Brain) (n=90, 56) 3.3 3.6
Complete Response (Outside Brain) (n=79, 40) 0.0 5.0
Partial Response (Outside Brain) (n=79, 40) 31.6 22.5
Stable Disease (Outside Brain) (n=79, 40) 49.4 52.5
Progressive Disease (Outside Brain) (n=79, 40) 11.4 15.0
Unevaluable (Outside Brain) (n=79, 40) 7.6 5.0
11.Secondary Outcome
Title Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Not Necessarily Follows the RECIST Criteria - as Assessed by Investigator)
Hide Description Percentage of participants who were responders (with best overall response (BOR) documented as confirmed complete response [CR] or partial response [PR]) were reported.
Time Frame Baseline up to the disease progression or death from any cause (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were enrolled in the study.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.9
(11.4 to 28.5)
17.9
(8.9 to 30.4)
12.Secondary Outcome
Title Percentage of Participants With Adverse Events (AE)
Hide Description An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug.
Time Frame From signing of informed consent form up to 28 days after the last dose of study drug (approximately up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study medication.
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description:
Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
Overall Number of Participants Analyzed 90 56
Measure Type: Number
Unit of Measure: percentage of participants
97.8 94.6
Time Frame From signing of informed consent form up to 28 days after the last dose of study drug (Up to approximately 4 years)
Adverse Event Reporting Description The safety population included all participants who received at least one dose of study medication.
 
Arm/Group Title Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Hide Arm/Group Description Participants who had not received previous treatment for brain metastases [i.e., had never received brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT), surgery, or any other treatment for their brain metastases] received Vemurafenib 960 milligram (mg) tablet orally, twice daily (BID) from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor. Participants who were previously treated with brain SRT, WBRT, or surgery for their brain metastases and have progressed following this treatment, received Vemurafenib 960 milligram (mg) tablet orally, BID from Day 1 until development of progressive disease within the brain or outside of the brain (whichever occurred first), unacceptable toxicity, consent withdrawal, protocol violation endangering participant’s safety, death, reasons deemed by the investigator, or study termination by the Sponsor.
All-Cause Mortality
Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Affected / at Risk (%) Affected / at Risk (%)
Total   37/90 (41.11%)   27/56 (48.21%) 
Blood and lymphatic system disorders     
Neutropenia  1  1/90 (1.11%)  0/56 (0.00%) 
Pancytopenia  1  0/90 (0.00%)  1/56 (1.79%) 
Cardiac disorders     
Cardiac failure acute  1  0/90 (0.00%)  1/56 (1.79%) 
Pericardial effusion  1  1/90 (1.11%)  0/56 (0.00%) 
Pericarditis constrictive  1  1/90 (1.11%)  0/56 (0.00%) 
Endocrine disorders     
Hyperthyroidism  1  1/90 (1.11%)  0/56 (0.00%) 
Eye disorders     
Iridocyclitis  1  0/90 (0.00%)  1/56 (1.79%) 
Ocular ischaemic syndrome  1  0/90 (0.00%)  1/56 (1.79%) 
Papilloedema  1  0/90 (0.00%)  1/56 (1.79%) 
Uveitis  1  0/90 (0.00%)  1/56 (1.79%) 
Gastrointestinal disorders     
Abdominal pain upper  1  2/90 (2.22%)  0/56 (0.00%) 
Ileus  1  1/90 (1.11%)  0/56 (0.00%) 
Intestinal obstruction  1  1/90 (1.11%)  0/56 (0.00%) 
General disorders     
Pyrexia  1  2/90 (2.22%)  0/56 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute  1  1/90 (1.11%)  0/56 (0.00%) 
Cholestasis  1  0/90 (0.00%)  1/56 (1.79%) 
Liver injury  1  0/90 (0.00%)  1/56 (1.79%) 
Infections and infestations     
Pneumonia  1  1/90 (1.11%)  2/56 (3.57%) 
Abscess rupture  1  0/90 (0.00%)  1/56 (1.79%) 
Bronchitis  1  0/90 (0.00%)  1/56 (1.79%) 
Bronchopneumonia  1  0/90 (0.00%)  1/56 (1.79%) 
Diabetic foot infection  1  1/90 (1.11%)  0/56 (0.00%) 
Diarrhoea infectious  1  0/90 (0.00%)  1/56 (1.79%) 
Post procedural cellulitis  1  1/90 (1.11%)  0/56 (0.00%) 
Post procedural infection  1  0/90 (0.00%)  1/56 (1.79%) 
Pyelonephritis  1  1/90 (1.11%)  0/56 (0.00%) 
Sepsis  1  0/90 (0.00%)  1/56 (1.79%) 
Streptococcal infection  1  0/90 (0.00%)  1/56 (1.79%) 
Investigations     
Alanine aminotransferase increased  1  1/90 (1.11%)  0/56 (0.00%) 
Aspartate aminotransferase increased  1  1/90 (1.11%)  0/56 (0.00%) 
Electrocardiogram QT prolonged  1  0/90 (0.00%)  1/56 (1.79%) 
Gamma-glutamyltransferase increased  1  1/90 (1.11%)  0/56 (0.00%) 
Hepatic enzyme increased  1  1/90 (1.11%)  0/56 (0.00%) 
Lipase increased  1  1/90 (1.11%)  0/56 (0.00%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc degeneration  1  1/90 (1.11%)  0/56 (0.00%) 
Muscular weakness  1  1/90 (1.11%)  0/56 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Squamous cell carcinoma of skin  1  11/90 (12.22%)  6/56 (10.71%) 
Keratoacanthoma  1  11/90 (12.22%)  4/56 (7.14%) 
Malignant melanoma  1  2/90 (2.22%)  2/56 (3.57%) 
Basal cell carcinoma  1  1/90 (1.11%)  0/56 (0.00%) 
Bowen's disease  1  0/90 (0.00%)  1/56 (1.79%) 
Glioma  1  1/90 (1.11%)  0/56 (0.00%) 
Intracranial tumour haemorrhage  1  0/90 (0.00%)  1/56 (1.79%) 
Squamous cell carcinoma  1  0/90 (0.00%)  1/56 (1.79%) 
Tonsillar neoplasm benign  1  0/90 (0.00%)  1/56 (1.79%) 
Nervous system disorders     
Haemorrhage intracranial  1  1/90 (1.11%)  1/56 (1.79%) 
Seizure  1  1/90 (1.11%)  1/56 (1.79%) 
Brain oedema  1  1/90 (1.11%)  0/56 (0.00%) 
Central nervous system haemorrhage  1  0/90 (0.00%)  1/56 (1.79%) 
Cerebral haemorrhage  1  1/90 (1.11%)  0/56 (0.00%) 
Epilepsy  1  1/90 (1.11%)  0/56 (0.00%) 
Headache  1  0/90 (0.00%)  1/56 (1.79%) 
Psychiatric disorders     
Confusional state  1  0/90 (0.00%)  2/56 (3.57%) 
Mental status changes  1  0/90 (0.00%)  1/56 (1.79%) 
Panic attack  1  0/90 (0.00%)  1/56 (1.79%) 
Renal and urinary disorders     
Nephrolithiasis  1  0/90 (0.00%)  1/56 (1.79%) 
Renal failure  1  0/90 (0.00%)  1/56 (1.79%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia aspiration  1  1/90 (1.11%)  0/56 (0.00%) 
Pulmonary embolism  1  1/90 (1.11%)  0/56 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash  1  1/90 (1.11%)  0/56 (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%
Cohort 1: Previously Untreated Participants Cohort 2: Previously Treated Participants
Affected / at Risk (%) Affected / at Risk (%)
Total   85/90 (94.44%)   53/56 (94.64%) 
Blood and lymphatic system disorders     
Anaemia  1  7/90 (7.78%)  6/56 (10.71%) 
Neutropenia  1  1/90 (1.11%)  3/56 (5.36%) 
Eye disorders     
Photophobia  1  2/90 (2.22%)  3/56 (5.36%) 
Visual impairment  1  1/90 (1.11%)  3/56 (5.36%) 
Gastrointestinal disorders     
Nausea  1  15/90 (16.67%)  14/56 (25.00%) 
Diarrhoea  1  14/90 (15.56%)  10/56 (17.86%) 
Vomoting  1  8/90 (8.89%)  8/56 (14.29%) 
Constipation  1  5/90 (5.56%)  2/56 (3.57%) 
Abdominal pain upper  1  1/90 (1.11%)  3/56 (5.36%) 
Dyspepsia  1  0/90 (0.00%)  3/56 (5.36%) 
Faecal incontinence  1  0/90 (0.00%)  3/56 (5.36%) 
General disorders     
Fatigue  1  22/90 (24.44%)  19/56 (33.93%) 
Asthenia  1  13/90 (14.44%)  6/56 (10.71%) 
Oedema peripheral  1  7/90 (7.78%)  8/56 (14.29%) 
Pyrexia  1  11/90 (12.22%)  7/56 (12.50%) 
Pain  1  6/90 (6.67%)  5/56 (8.93%) 
Chest Pain  1  1/90 (1.11%)  4/56 (7.14%) 
Xerosis  1  5/90 (5.56%)  1/56 (1.79%) 
Immune system disorders     
Contrast media allergy  1  0/90 (0.00%)  3/56 (5.36%) 
Infections and infestations     
Nasopharyngitis  1  5/90 (5.56%)  4/56 (7.14%) 
Upper respiratory tract infection  1  2/90 (2.22%)  4/56 (7.14%) 
Urinary tract infection  1  2/90 (2.22%)  4/56 (7.14%) 
Conjunctivitis  1  2/90 (2.22%)  3/56 (5.36%) 
Folliculitis  1  0/90 (0.00%)  3/56 (5.36%) 
Injury, poisoning and procedural complications     
Sunburn  1  6/90 (6.67%)  2/56 (3.57%) 
Investigations     
Electrocardiogram QT prolonged  1  22/90 (24.44%)  8/56 (14.29%) 
Aspartate aminotransferase increased  1  6/90 (6.67%)  3/56 (5.36%) 
Blood bilirubin increased  1  6/90 (6.67%)  4/56 (7.14%) 
Alanine aminotransferase increased  1  6/90 (6.67%)  5/56 (8.93%) 
Blood alkaline phosphatase increased  1  5/90 (5.56%)  2/56 (3.57%) 
Weight decreased  1  6/90 (6.67%)  6/56 (10.71%) 
Blood creatinine increased  1  5/90 (5.56%)  3/56 (5.36%) 
Metabolism and nutrition disorders     
Decreased appetite  1  8/90 (8.89%)  3/56 (5.36%) 
Hypokalaemia  1  2/90 (2.22%)  5/56 (8.93%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  31/90 (34.44%)  23/56 (41.07%) 
Pain in extremity  1  8/90 (8.89%)  5/56 (8.93%) 
Myalgia  1  8/90 (8.89%)  5/56 (8.93%) 
Musculoskeletal pain  1  6/90 (6.67%)  3/56 (5.36%) 
Back pain  1  5/90 (5.56%)  1/56 (1.79%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin papilloma  1  15/90 (16.67%)  12/56 (21.43%) 
Seborrhoeic keratosis  1  7/90 (7.78%)  1/56 (1.79%) 
Basal cell carcinoma  1  1/90 (1.11%)  3/56 (5.36%) 
Nervous system disorders     
Headache  1  16/90 (17.78%)  8/56 (14.29%) 
Paraesthesia  1  9/90 (10.00%)  2/56 (3.57%) 
Dysgeusia  1  6/90 (6.67%)  4/56 (7.14%) 
Seizure  1  2/90 (2.22%)  6/56 (10.71%) 
Dizziness  1  3/90 (3.33%)  3/56 (5.36%) 
Balance disorder  1  0/90 (0.00%)  3/56 (5.36%) 
Tremor  1  0/90 (0.00%)  5/56 (8.93%) 
Psychiatric disorders     
Insomnia  1  5/90 (5.56%)  7/56 (12.50%) 
Confusional state  1  0/90 (0.00%)  4/56 (7.14%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  8/90 (8.89%)  6/56 (10.71%) 
Dyspnoea  1  5/90 (5.56%)  3/56 (5.36%) 
Oropharyngeal pain  1  3/90 (3.33%)  3/56 (5.36%) 
Skin and subcutaneous tissue disorders     
Hyperkeratosis  1  28/90 (31.11%)  13/56 (23.21%) 
Rash  1  29/90 (32.22%)  17/56 (30.36%) 
Photosensitivity Reaction  1  18/90 (20.00%)  17/56 (30.36%) 
Erythema  1  13/90 (14.44%)  9/56 (16.07%) 
Palmar-plantar erythrodysaesthesia syndrome  1  7/90 (7.78%)  8/56 (14.29%) 
Alopecia  1  16/90 (17.78%)  13/56 (23.21%) 
Pruritus  1  16/90 (17.78%)  6/56 (10.71%) 
Dry skin  1  11/90 (12.22%)  10/56 (17.86%) 
Actinic keratosis  1  6/90 (6.67%)  5/56 (8.93%) 
Keratosis pilaris  1  9/90 (10.00%)  2/56 (3.57%) 
Dermal cyst  1  4/90 (4.44%)  3/56 (5.36%) 
Rash follicular  1  1/90 (1.11%)  3/56 (5.36%) 
Vascular disorders     
Hypertension  1  6/90 (6.67%)  4/56 (7.14%) 
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
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01378975     History of Changes
Other Study ID Numbers: MO25743
First Submitted: June 21, 2011
First Posted: June 23, 2011
Results First Submitted: June 20, 2016
Results First Posted: August 1, 2016
Last Update Posted: August 1, 2016