Back to resultsA Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases
Primary Purpose
Malignant Melanoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Vemurafenib
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Melanoma
Eligibility Criteria
Inclusion Criteria:
- Adult participants, >/= 18 years of age
- Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) with BRAF V600 mutation (cobas 4800 BRAF V600 Mutation Test)
- Measurable brain metastases, defined as lesions that were accurately measured in at least one dimension (longest diameter to be recorded) as ≥0.5 cm in the brain MRI with contrast, treated or untreated
- Participants may or may not have received prior systemic therapy for metastatic melanoma and either a) have received no prior treatment for brain metastases or b) have received prior treatment for brain metastases and have progressed
- Participants may or may not have symptoms related to their brain metastases
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Participants must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma
Exclusion Criteria:
- Increasing corticosteroid dose during the 7 days prior to first dose of study drug
- Leptomeningeal involvement in participants with no prior treatment for brain metastases
- Previous malignancy requiring active treatment within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix
- Concurrent administration of any anticancer therapies other than those administered in the study
- Treatment with any cytotoxic, investigational drug or targeted therapy 4 weeks prior to first dose of study drug. Radiation therapy ≤1 week prior to first administration of vemurafenib; and stereotactic radiotherapy ≤1 day prior to prior to first administration of vemurafenib
- Prior treatment with BRAF or MEK inhibitors
- Clinically significant cardiovascular disease or event within the 6 months prior to first dose of study drug
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1: Previously Untreated Participants
Cohort 2: Previously treated Participants
Arm 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.
Outcomes
Primary Outcome Measures
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])
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.
Secondary Outcome Measures
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
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.
Best Overall Response Rate (BORR) in the Brain of Participants With Previously Treated Brain Metastases as Assessed by the IRC Using RECIST v1.1
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.
Best Overall Response Rate Outside the Brain (Assessed by IRC)
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.
Duration of Response (DOR) (Assessed by Investigator and IRC)
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.
Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator)
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.
Progression-Free Survival (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator )
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 to Development of New Brain Metastases in Responders
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.
Overall Survival
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.
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator)
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.
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Not Necessarily Follows the RECIST Criteria - as Assessed by Investigator)
Percentage of participants who were responders (with best overall response (BOR) documented as confirmed complete response [CR] or partial response [PR]) were reported.
Percentage of Participants With Adverse Events (AE)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01378975
Brief Title
A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases
Official Title
An Open-label, Single-arm, Phase II, Multicenter Study, to Evaluate the Efficacy of Vemurafenib in Metastatic Melanoma Patients With Brain Metastases
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
July 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
Brief Summary
This open-label, single-arm, multicenter study will evaluate the efficacy and safety in participants with metastatic melanoma who developed brain metastases. Participants may or may not have received prior systemic treatment for metastatic melanoma [except treatment with v-raf murine sarcoma viral oncogene homolog B (BRAF) or mitogen-activated protein kinase (MEK) inhibitors]. Participants will receive oral doses of 960 mg vemurafenib twice daily until disease progression, unacceptable toxicity or consent withdrawal.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
146 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Previously Untreated Participants
Arm Type
Experimental
Arm 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.
Arm Title
Cohort 2: Previously treated Participants
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Vemurafenib
Intervention Description
960 mg oral doses twice daily until disease progression, unacceptable toxicity or consent withdrawal.
Primary Outcome Measure Information:
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])
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)
Secondary Outcome Measure Information:
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
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)
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
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)
Title
Best Overall Response Rate Outside the Brain (Assessed by IRC)
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)
Title
Duration of Response (DOR) (Assessed by Investigator and IRC)
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)
Title
Progression-Free Survival (PFS) Based on Overall Tumor Response (Assessed by Investigator)
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)
Title
Progression-Free Survival (PFS) Based on Tumor Assessment Within Brain Only (Assessed by Investigator )
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)
Title
Time to Development of New Brain Metastases in Responders
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)
Title
Overall Survival
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)
Title
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Assessed by Investigator)
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)
Title
Best Overall Response Rate (BORR) Within the Brain and Outside Brain (Not Necessarily Follows the RECIST Criteria - as Assessed by Investigator)
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)
Title
Percentage of Participants With Adverse Events (AE)
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult participants, >/= 18 years of age
Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) with BRAF V600 mutation (cobas 4800 BRAF V600 Mutation Test)
Measurable brain metastases, defined as lesions that were accurately measured in at least one dimension (longest diameter to be recorded) as ≥0.5 cm in the brain MRI with contrast, treated or untreated
Participants may or may not have received prior systemic therapy for metastatic melanoma and either a) have received no prior treatment for brain metastases or b) have received prior treatment for brain metastases and have progressed
Participants may or may not have symptoms related to their brain metastases
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Participants must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma
Exclusion Criteria:
Increasing corticosteroid dose during the 7 days prior to first dose of study drug
Leptomeningeal involvement in participants with no prior treatment for brain metastases
Previous malignancy requiring active treatment within the past 2 years, except for treated and controlled basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix
Concurrent administration of any anticancer therapies other than those administered in the study
Treatment with any cytotoxic, investigational drug or targeted therapy 4 weeks prior to first dose of study drug. Radiation therapy ≤1 week prior to first administration of vemurafenib; and stereotactic radiotherapy ≤1 day prior to prior to first administration of vemurafenib
Prior treatment with BRAF or MEK inhibitors
Clinically significant cardiovascular disease or event within the 6 months prior to first dose of study drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204-2839
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
City
Wentworthville
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
City
Bordeaux
ZIP/Postal Code
33075
Country
France
City
Nice
ZIP/Postal Code
06202
Country
France
City
Paris
ZIP/Postal Code
75006
Country
France
City
Paris
ZIP/Postal Code
75475
Country
France
City
Essen
ZIP/Postal Code
45122
Country
Germany
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
City
Kiel
ZIP/Postal Code
24105
Country
Germany
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
City
Münster
ZIP/Postal Code
48157
Country
Germany
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
City
Tel-Hashomer
ZIP/Postal Code
52621
Country
Israel
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
City
Siena
State/Province
Toscana
ZIP/Postal Code
53100
Country
Italy
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Madrid
ZIP/Postal Code
28046
Country
Spain
City
Northwood
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases
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