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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01378975




Registration number
NCT01378975
Ethics application status
Date submitted
21/06/2011
Date registered
23/06/2011
Date last updated
1/08/2016

Titles & IDs
Public title
A Study of Vemurafenib in Metastatic Melanoma Participants With Brain Metastases
Scientific title
An Open-label, Single-arm, Phase II, Multicenter Study, to Evaluate the Efficacy of Vemurafenib in Metastatic Melanoma Patients With Brain Metastases
Secondary ID [1] 0 0
MO25743
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Vemurafenib

Experimental: Cohort 1: Previously Untreated Participants - 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.

Experimental: Cohort 2: Previously treated Participants - 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.


Treatment: Drugs: Vemurafenib
960 mg oral doses twice daily until disease progression, unacceptable toxicity or consent withdrawal.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Date of the earliest qualifying response until the earliest date of PD or death from any cause (approximately up to 4 years)
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Date of first treatment and the earliest date of documentation of new brain lesions (approximately up to 4 years)
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline up to the disease progression or death from any cause (approximately 4 years)
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
From signing of informed consent form up to 28 days after the last dose of study drug (approximately up to 4 years)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Wentworthville
Recruitment hospital [2] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Wentworthville
Recruitment postcode(s) [2] 0 0
3002 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Washington
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
France
State/province [12] 0 0
Bordeaux
Country [13] 0 0
France
State/province [13] 0 0
Nice
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
Germany
State/province [15] 0 0
Essen
Country [16] 0 0
Germany
State/province [16] 0 0
Frankfurt
Country [17] 0 0
Germany
State/province [17] 0 0
Kiel
Country [18] 0 0
Germany
State/province [18] 0 0
Mannheim
Country [19] 0 0
Germany
State/province [19] 0 0
Münster
Country [20] 0 0
Germany
State/province [20] 0 0
Tübingen
Country [21] 0 0
Israel
State/province [21] 0 0
Tel-Hashomer
Country [22] 0 0
Italy
State/province [22] 0 0
Lombardia
Country [23] 0 0
Italy
State/province [23] 0 0
Toscana
Country [24] 0 0
Netherlands
State/province [24] 0 0
Amsterdam
Country [25] 0 0
Netherlands
State/province [25] 0 0
Groningen
Country [26] 0 0
Spain
State/province [26] 0 0
Navarra
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Northwood

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01378975
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications