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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01153763
Registration number
NCT01153763
Ethics application status
Date submitted
27/05/2010
Date registered
30/06/2010
Date last updated
27/09/2017
Titles & IDs
Public title
A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma
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Scientific title
A Phase II (BRF113710) Single-arm, Open-label Study of GSK2118436 in BRAF Mutant Metastatic Melanoma
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Secondary ID [1]
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113710
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - GSK2118436
Other: All patients - Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.
Treatment: Drugs: GSK2118436
Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator for Participants Who Had a BRAF V600E Mutation
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Assessment method [1]
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A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeter (mm) in the short axis.) or PR (at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). To be assigned a status of PR or CR, a confirmatory disease assessment was required at Week 12 if an initial response was seen at the Week 6 scan. Initial responses (CR/PR) that occured at Week 12 or later were required to be confirmed not less than 4 weeks and not more than 6 weeks after the criteria for response were first met. The analysis was performed on Primary efficacy Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600E mutation.
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Timepoint [1]
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Up to 60 months
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Secondary outcome [1]
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Number of Participants With a Best Overall Response of CR or PR as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
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Assessment method [1]
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A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). To be assigned a status of PR or CR, a confirmatory disease assessment had to have been performed at Week 12 if an initial response was seen at the Week 6 scan. Initial responses (CR/PR) that occured at Week 12 or later should have been confirmed not less than 4 weeks and not more than 6 weeks after the criteria for response were first met. The analysis was performed on Secondary efficacy analysis Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600K mutation.
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Timepoint [1]
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Up to 60 months
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Secondary outcome [2]
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Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation
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Assessment method [2]
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PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or progression minus date of first dose plus 1 day. Kaplan-Meier model was used to estimate the median and 95 percent confidence interval (CI). For participants who received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was censored at the last adequate assessment. For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.
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Timepoint [2]
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Up to 60 months
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Secondary outcome [3]
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Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
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Assessment method [3]
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PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or progression minus date of first dose plus 1 day. Kaplan-Meier model was used to estimate the median and 95 percent CI. For participants who received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was censored at the last adequate assessment. For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.
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Timepoint [3]
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Up to 60 months
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Secondary outcome [4]
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Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation
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Assessment method [4]
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Duration of response for participants with either a CR or PR is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. Duration of response was estimated using Kaplan-Meier model and the median and 95 percent CI was presented. The analysis was performed on Primary efficacy Population and only those participants who had a CR or PR were analyzed.
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Timepoint [4]
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Up to 60 months
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Secondary outcome [5]
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Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
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Assessment method [5]
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Duration of response for participants with either a CR or PR is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. Duration of response was estimated using Kaplan-Meier model and the median and 95 percent CI was presented. The analysis was performed on Secondary efficacy Population and only those participants who had a CR or PR were analyzed.
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Timepoint [5]
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Up to 60 months
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Secondary outcome [6]
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Overall Survival for Participants Who Had a BRAF V600E Mutation
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Assessment method [6]
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Overall survival is defined as the time from the first dose of study medication until death due to any cause. For participants who did not die, overall survival was censored at the date of last contact. Overall survival was estimated using kaplan-Meier model and median and 95 percent CI was presented.
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Timepoint [6]
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Up to 60 months
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Secondary outcome [7]
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Overall Survival for Participants Who Had a BRAF V600K Mutation
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Assessment method [7]
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Overall survival is defined as the time from the first dose of study medication until death due to any cause. For participants who did not die, overall survival was censored at the date of last contact. Overall survival was estimated using Kaplan-Meier model and median and 95 percent CI was presented.
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Timepoint [7]
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From the first dose to death due to any cause (up to 60 months)
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Secondary outcome [8]
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Number of Participants With AEs and Serious Adverse Events (SAEs)
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Assessment method [8]
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An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs including systemic allergic and non-allergic reactions as well as local site injection-related reactions were counted throughout treatment phase and follow up phase. Systemic allergic reactions included facial paralysis, flushing, hypersensitivity and rash pruritic. Injection related reactions were considered as systemic non-allergic reactions. Local site reactions included injection site bruising, erythema, pain and reaction. The analysis was performed on All treated Population which comprised of all participants that receive at least one dose of dabrafenib.
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Timepoint [8]
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Up to 60 months
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Secondary outcome [9]
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Number of Participants With Change From Baseline in Clinical Chemistry and Hematology Toxicity Grades
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Assessment method [9]
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Blood samples were collected from participants for evaluation of change from Baseline in toxicity grades in clinical chemistry and hematology parameters. The clinical chemistry parameters included alkaline phosphatase, Alanine amino transferase (ALT), Aspartate amino transferase (AST), total bilirubin, creatinine, glucose, potassium, magnesium, sodium and phosphorus. The hematology parameters included hemoglobin, total neutrophils, platelets and white blood cells (WBC). Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst case post-baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
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Timepoint [9]
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Up to 60 months
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Secondary outcome [10]
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Number of Participants With Change From Baseline in Temperature and Pulse Rate
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Assessment method [10]
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Number of participants with change from Baseline in temperature and pulse rate were evaluated from the first dose of study treatment till discontinuation due to any reason. Change from Baseline in worst-case post Baseline value was presented as decrease to <=35, change to normal or no change and increase to >=38. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst case post-baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period.
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Timepoint [10]
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Up to 60 months
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Secondary outcome [11]
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Number of Participants With Increase From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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Assessment method [11]
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Number of participants with increase from Baseline in SBP and DBP were evaluated from the first dose of study treatment till discontinuation due to any reason. Change from Baseline in worst-case post Baseline value was presented as any increase to >=80 and increase to >=100 for DBP and as any increase to >=120 and increase to >=160 for SBP. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst-case post Baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period. One participant out of the 92 participants (76 BRAF V600E patients + 16 BRAF V600K patients) did not have SBP and DBP collected after baseline.
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Timepoint [11]
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Up to 60 months
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Secondary outcome [12]
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Number of Participants With Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Levels
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Assessment method [12]
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LVEF was defined as the percentage of blood pumped out of the left ventricle. Change from Baseline in worst-case post Baseline was presented as no change or any increase and any decrease values. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst-case post Baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period.
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Timepoint [12]
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Up to 60 months
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Eligibility
Key inclusion criteria
- Must be at least 18 years of age
- Must have histologically confirmed cutaneous metastatic melanoma (Stage IV) that is
BRAF mutation-positive (V600 E/K) as determined via central testing with a BRAF
mutation assay.
- Is treatment naive or has received prior treatment for metastatic melanoma.
- Must have measurable disease according to Response Evaluation Criteria in Solid Tumors
(RECIST 1.1).
- Women of child-bearing potential must have a negative pregnancy test within 14 days
prior to the first dose of study treatment.
- Women with reproductive potential must be willing to practice acceptable methods of
birth control during the study and for up to 4 weeks after the last dose of study
medication.
- Men with reproductive potential must be willing to practice acceptable methods of
birth control during the study and for up to 16 weeks after the last dose of study
medication.
- Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Adequate organ function.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Previous treatment with a BRAF or MEK inhibitor.
- Cancer therapy (chemotherapy with delayed toxicity, radiation therapy, immunotherapy,
biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens
without delayed toxicity within the last 2 weeks; or use of any investigational
anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer,
preceding the first dose of GSK2118436.
- A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or
Hepatitis C Virus (HCV) infection.
- History or evidence of brain metastases on MRI or head CT if MRI is not able to be
performed.
- History of other malignancy. Subjects who have been disease-free for 5 years, or
subjects with a history of completely resected non-melanoma skin cancer or
successfully treated in situ carcinoma are eligible.
- Certain cardiac abnormalities.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
9/08/2010
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/06/2016
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Sample size
Target
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Accrual to date
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Final
92
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Recruitment in Australia
Recruitment state(s)
NSW,WA
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Recruitment hospital [1]
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GSK Investigational Site - Newcastle
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Recruitment hospital [2]
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GSK Investigational Site - Westmead
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Recruitment hospital [3]
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GSK Investigational Site - Nedlands
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Recruitment postcode(s) [1]
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2300 - Newcastle
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Recruitment postcode(s) [2]
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2145 - Westmead
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Recruitment postcode(s) [3]
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6009 - Nedlands
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Pennsylvania
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Country [3]
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United States of America
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State/province [3]
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Tennessee
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Country [4]
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United States of America
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State/province [4]
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Texas
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Country [5]
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France
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State/province [5]
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Bordeaux
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Country [6]
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France
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State/province [6]
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Boulogne-Billancourt
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Country [7]
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France
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State/province [7]
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Lille
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Country [8]
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France
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State/province [8]
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Marseille Cedex 5
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Country [9]
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France
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State/province [9]
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Montpellier
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Country [10]
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France
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State/province [10]
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Paris Cedex 10
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Country [11]
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France
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State/province [11]
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Villejuif
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Country [12]
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Germany
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State/province [12]
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Nordrhein-Westfalen
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Country [13]
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Germany
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State/province [13]
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Schleswig-Holstein
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Country [14]
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Germany
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State/province [14]
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Berlin
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Country [15]
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Italy
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State/province [15]
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Campania
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Country [16]
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Italy
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State/province [16]
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Liguria
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Country [17]
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Italy
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State/province [17]
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Veneto
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
GlaxoSmithKline
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
BRF113710 is a Phase II, single-arm, open-label study to assess the efficacy, safety, and
tolerability of GSK2118436 administered twice daily as a single agent in subjects with BRAF
mutant metastatic melanoma. Subjects will receive 150 mg of GSK2118436 twice daily and
continue on treatment until disease progression, death, or unacceptable adverse event.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01153763
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Trial related presentations / publications
Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, Guckert M, Schadendorf D, Kefford RF, Grob JJ, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim KB, Long GV, Martin AM, Mazumdar J, Goodman VL, Trefzer U. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. 2013 Sep 10;31(26):3205-11. doi: 10.1200/JCO.2013.49.8691. Epub 2013 Aug 5.
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Public notes
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Contacts
Principal investigator
Name
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GSK Clinical Trials
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Address
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GlaxoSmithKline
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01153763
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