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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01266967




Registration number
NCT01266967
Ethics application status
Date submitted
2/12/2010
Date registered
24/12/2010
Date last updated
8/05/2014

Titles & IDs
Public title
A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma to the Brain
Scientific title
BRF113929: An Open-Label, Two-Cohort, Multicentre Study of GSK2118436 as a Single Agent in Treatment Naïve and Previously Treated Subjects With BRAF Mutation-Positive Metastatic Melanoma to the Brain
Secondary ID [1] 0 0
113929
Universal Trial Number (UTN)
Trial acronym
Break MB
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma and Brain Metastases 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 - GSK2118436

Experimental: Single Arm - Single arm with 2 cohorts; Cohort A no previous brain therapy and Cohort B previous brain therapy


Treatment: Drugs: GSK2118436
Subjects in this study receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.

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

Outcomes
Primary outcome [1] 0 0
Number of Participants With BRAF V600E Mutation-positive Melanoma With Overall Intracranial Response (OIR), as Assessed by the Investigator
Timepoint [1] 0 0
From the time of the Baseline assessment until disease progression or end of study treatment (average of 18.3 weeks)
Secondary outcome [1] 0 0
Number of Participants With V600E Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator
Timepoint [1] 0 0
From the time of the Baseline assessment until disease progression or end of study treatment (average of 24 weeks)
Secondary outcome [2] 0 0
Number of Participants With V600K Mutation-positive Melanoma With a Best Overall Response (OR) of CR or PR, as Assessed by the Investigator
Timepoint [2] 0 0
From the time of the Baseline assessment until disease progression or end of study treatment (average of 17 weeks)
Secondary outcome [3] 0 0
Number of Participants With V600K Mutation-positive Melanoma With OIR, as Assessed by the Investigator
Timepoint [3] 0 0
From the time of the Baseline assessment until disease progression or end of study treatment (average of 16 weeks)
Secondary outcome [4] 0 0
Duration of Intracranial Response for the Subset of V600E Mutation-positive Participants
Timepoint [4] 0 0
Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 27 weeks)
Secondary outcome [5] 0 0
Duration of Intracranial Response for the Subset of V600K Mutation-positive Participants
Timepoint [5] 0 0
Time from the first documented evidence of intracranial CR or PR until the time of the first documented intracranial disease progression or death due to any cause (average of 31 weeks)
Secondary outcome [6] 0 0
Duration of Overall Response for the Subset of V600E Mutation-positive Participants
Timepoint [6] 0 0
Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 28 weeks)
Secondary outcome [7] 0 0
Duration of Overall Response for the Subset of V600K Mutation-positive Participants
Timepoint [7] 0 0
Time from the first documented evidence of CR or PR until the time of the first documented disease progression or death due to any cause (average of 31 weeks)
Secondary outcome [8] 0 0
Progression-free Survival in V600E Mutation-positive Participants
Timepoint [8] 0 0
Time from the first dose of study medication to the earliest of death or progression (average of 23 weeks)
Secondary outcome [9] 0 0
Progression-free Survival in V600K Mutation-positive Participants
Timepoint [9] 0 0
Time from the first dose of study medication to the earliest of death or progression (average of 17 weeks)
Secondary outcome [10] 0 0
Overall Survival of V600E Mutation-positive Participants
Timepoint [10] 0 0
Time from the first dose of study medication until death due to any cause (average of 35 weeks)
Secondary outcome [11] 0 0
Overall Survival in V600K Mutation-positive Participants
Timepoint [11] 0 0
Time from the first dose of study medication until death due to any cause (average of 26 weeks)
Secondary outcome [12] 0 0
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
Timepoint [12] 0 0
From Screening until the conclusion of the study (up to 103 weeks)
Secondary outcome [13] 0 0
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Clinical Chemistry Parameters
Timepoint [13] 0 0
From Screening until the conclusion of the study (up to 103 weeks)
Secondary outcome [14] 0 0
Number of Participants With the Indicated Hepatobiliary Laboratory Abnormalities
Timepoint [14] 0 0
From Screening until the conclusion of the study (up to 103 weeks)
Secondary outcome [15] 0 0
Number of Participants With a Worst-case on Therapy Change to Grade 3 and Grade 4, or With Any Grade Increase (AGI), From Baseline Grade for Hematology Parameters
Timepoint [15] 0 0
From Screening until the conclusion of the study (up to 103 weeks)
Secondary outcome [16] 0 0
Mean Blood Pressure at Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36
Timepoint [16] 0 0
Baseline; Weeks 4, 8, 12, 16, 20, 24, 28, 32, and 36
Secondary outcome [17] 0 0
Number of Participants With a Worst-case On-therapy Increase From Baseline in Bazett's QTc Reading in the 12-lead Electrocardiogram (ECG)
Timepoint [17] 0 0
Baseline; Weeks 4, 12, 20, 28, 40, 52, and 64
Secondary outcome [18] 0 0
Number of Participants With Abnormal Echocardiograms (ECHO) at Weeks 4 and 12
Timepoint [18] 0 0
Weeks (W) 4 and 12
Secondary outcome [19] 0 0
Median Concentrations of GSK2118436 and Its Metabolites Including GSK2285403, GSK2298683, and GSK2167542
Timepoint [19] 0 0
Week 4 (pre-dose and 1-3 hours post-dose) and Weeks 8, 16, 24, and 32 (either pre-dose in the morning or in the afternoon at 4-8 hours post-dose)
Secondary outcome [20] 0 0
Composite of Pharmacokinetic Parameters of GSK2118436 in a Subset of Participants Receiving Dexamethasone
Timepoint [20] 0 0
Day 15
Secondary outcome [21] 0 0
Number of Response Genetics Incorporated (RGI) Investigational Use Only (IUO) Assay Mutation Positive Participants and THxID BRAF Assay Mutation Positive Participants With the Indicated Best Intracranial Response
Timepoint [21] 0 0
Screening

Eligibility
Key inclusion criteria
* Cohort A:
* No prior local therapy for brain metastases.
* Subjects who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 3 weeks prior to first dose of study treatment.
* No prophylactic or preventive anti-epileptic therapy. Exception: anti-epileptic therapy indicated in order to prevent neurologic symptoms caused by a pre-existing condition and not related to brain metastasis is allowed.
* Cohort B:
* Subjects must have received at least one local therapy for brain metastases including but not restricted to brain surgery, Whole Brain Radiotherapy or Stereotactic Radiosurgery (e.g. gamma knife, linear-accelerated-based radiosurgery, charged particles, and CyberKnife). Multiple local therapies or combinations of local therapies are allowed. For subjects receiving local therapy to all brain lesions (including WBRT), progression of pre-existing lesions based on RECIST 1.1 (> 20% increase in longest diameter on baseline scan) or new measurable lesions are required. For subjects receiving local therapy for some but not all lesions, disease progression based on RECIST 1.1 is not required as long as there are remaining brain lesions that are measurable and not previously treated.
* Subjects who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 2 weeks prior to first dose of study treatment.
* Prophylactic or preventive anti-epileptic therapy is allowed.
* General:
* Must sign written informed consent.
* Must be at least 18 years of age.
* Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600E- or V600K-mutation.
* Up to two previous treatment regimens for extracranial metastatic melanoma including chemo-, cytokine-, immuno-, biological- and vaccine-therapy.
* At least one measurable intracranial target lesion for which all of the following criteria have to be met:
* previously untreated or progressive according to RECIST 1.1 (greater than or equal to 20% increase in longest diameter on baseline scan) after previous local therapy
* immediate local therapy clinically not indicated or patient is not a suitable candidate to receive immediate local therapy
* largest diameter of greater than or equal to 0.5cm but less than or equal to 4 cm as determined by contrast-enhanced MRI
* for target lesions (for definition see Section 6.1.1) with diameter of greater than 0.5 cm but less than or equal to 1 cm documented measurement by a neuroradiologist is required.
* for all lesions with diameter of greater than or equal to 3 cm but less than or equal to 4 cm documented measurement by a neuroradiologist is required.
* Time interval between last day of previous anti-tumour systemic treatment and first dose of GSK2118436:
* 14 days elapsed from last treatment with surgery, SRS or gamma knife
* 28 days elapsed from last treatment with WBRT
* Greater than or equal to 28 days or five half-lives (whichever is longer) have elapsed from last dose of approved or investigational chemo-, cytokine-, immune-, biological-, or vaccine-therapy.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
* Adequate organ function.
* Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study.
* Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Neurological symptoms related to brain metastasis.
* Previous treatment with a BRAF or MEK inhibitor.
* Current or expected use of a prohibited medication during treatment with GSK2118436.
* Presence of leptomeningeal disease or primary dural metastases.
* Known allergies against contrast agents required for magnetic resonance imaging (MRI) of intracranial lesions.
* Current use of therapeutic warfarin. NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted.
* Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI v4.0) Grade 2 or higher from previous anti-cancer therapy, except alopecia.
* Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs.
* A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
* Acute infection requiring intravenous antibiotics
* History of another malignancy. Exception: (a) Subjects who have been disease-free for 5 years, (b) a history of completely resected non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer requiring no or only anti-hormonal therapy with histologically confirmed tumour lesions that can be clearly differentiated from melanoma target and non-target lesions are eligible.
* Certain cardiac abnormalities.

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
Single group
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,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Waratah
Recruitment hospital [2] 0 0
GSK Investigational Site - Westmead
Recruitment hospital [3] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
2300 - Waratah
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
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
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
Canada
State/province [8] 0 0
Alberta
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
France
State/province [11] 0 0
Boulogne-Billancourt
Country [12] 0 0
France
State/province [12] 0 0
Lille
Country [13] 0 0
France
State/province [13] 0 0
Marseille Cedex 5
Country [14] 0 0
France
State/province [14] 0 0
Villejuif
Country [15] 0 0
Germany
State/province [15] 0 0
Nordrhein-Westfalen
Country [16] 0 0
Germany
State/province [16] 0 0
Schleswig-Holstein
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Italy
State/province [18] 0 0
Campania
Country [19] 0 0
Italy
State/province [19] 0 0
Veneto

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.