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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/NCT01227889
Registration number
NCT01227889
Ethics application status
Date submitted
21/10/2010
Date registered
25/10/2010
Date last updated
4/10/2017
Titles & IDs
Public title
A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma
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Scientific title
A Phase III Randomized, Open-label Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma
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Secondary ID [1]
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0
113683
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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:
Cancer
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Condition category
Condition code
Cancer
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0
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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
Treatment: Drugs - Dacarbazine (DTIC)
Experimental: GSK2118436 - Subjects in this arm will receive GSK2118436 150 mg twice daily.
Active Comparator: Dacarbazine (DTIC) - Subjects will receive intravenous dacarbazine (DTIC) 1000 mg/m2 every 3 weeks
Experimental: Crossover - Subjects who initially receive DTIC will be allowed to receive GSK2118436 after initial progression.
Treatment: Drugs: GSK2118436
150 mg twice daily
Treatment: Drugs: Dacarbazine (DTIC)
Intravenous (IV), 1000 mg/m2 every 3 weeks until initial progression
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Intervention code [1]
0
0
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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Progression-free Survival (PFS) as Assessed by the Investigator
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Assessment method [1]
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PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). For participants who did not progress or die, PFS was censored at the date of last contact. Data are presented as median and 96% confidence interval.
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Timepoint [1]
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Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months)
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Primary outcome [2]
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Progression-free Survival (PFS) as Assessed by an Independent Radiologist: Randomized Phase
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Assessment method [2]
0
0
PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by an independent radiologist according to RECIST version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact.
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Timepoint [2]
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Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months)
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Secondary outcome [1]
0
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Overall Survival
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Assessment method [1]
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0
Overall survival is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, overall survival was censored at the date of last contact.
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Timepoint [1]
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Time interval between the date of randomization and the date of death due to any cause (up to 22.1 months)
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Secondary outcome [2]
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Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Randomized Phase
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Assessment method [2]
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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% 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]). Response was evaluated by an investigator per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR.
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Timepoint [2]
0
0
From randomization until the first documented evidence of a confirmed complete response or partial response (median of 6.6 weeks)
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Secondary outcome [3]
0
0
Number of Participants With a Best Overall Response of Confirmed CR or PR as Assessed by an Independent Radiologist: Randomized Phase
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Assessment method [3]
0
0
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% 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]). Response was evaluated by an independent radiologist per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR.
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Timepoint [3]
0
0
From randomization until the first documented evidence of a confirmed complete response or partial response (median of 12.0 weeks)
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Secondary outcome [4]
0
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Duration of Response as Assessed by the Investigator: Randomized Phase
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Assessment method [4]
0
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Duration of response for participants with 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% 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]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of PD or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm.
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Timepoint [4]
0
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Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 65.6 weeks)
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Secondary outcome [5]
0
0
Duration of Response as Assessed by an Independent Radiologist: Randomized Phase
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Assessment method [5]
0
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Duration of response for participants with 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% 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]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of PD or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. NA indicates that data is not available.
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Timepoint [5]
0
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Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 7.4 months)
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Secondary outcome [6]
0
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Progression-free Survival (PFS2) as Assessed by the Investigator: Crossover Phase
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Assessment method [6]
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PFS2 is defined as the time from the first dose of GSK2118436, in participants randomized to DTIC who crossed over to GSK2118436 after initial progression, to the earliest date of radiographic or photographic disease progression or death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact.
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Timepoint [6]
0
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Time from first dose of GSK2118436 in participants who crossover after initial progression to the earliest date of radiographical or photographical PD or death due to any cause (up to 6.4 months)
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Secondary outcome [7]
0
0
Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the Investigator: Crossover Phase
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Assessment method [7]
0
0
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% 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]). Response was evaluated by an investigator per RECIST, version 1.1. A participant without a post-Baseline assessment of response was considered a non-responder. Confirmation, per RECIST version 1.1, requires a confimatory disease assessment of CR or PR at least 28 days after the initial disease assessment of CR or PR.
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Timepoint [7]
0
0
From randomization until the first documented evidence of a confirmed complete response or partial response (up to 6.4 months)
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Secondary outcome [8]
0
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Duration of Response as Assessed by the Investigator: Crossover Phase
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Assessment method [8]
0
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Duration of response for participants with 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% 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]) was defined as the time from the first documented evidence of a PR or CR until the first documented sign of PD or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm.
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Timepoint [8]
0
0
Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 6.4 months)
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Secondary outcome [9]
0
0
Number of Participants With Non-melanoma Skin Lesions: Randomized Phase
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Assessment method [9]
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Dermatological examinations were performed by the investigator, or at the discretion of the investigator, referred to a dermatologist. The number of participants with non-melanoma skin lessions was assessed from the time of Screening until study completion or discontinuation from the study for any reason.
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Timepoint [9]
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0
From Screening until study completion or discontinuation from the study (up to 9.9 months)
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Secondary outcome [10]
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0
Agreement Rate for V600E Mutation Validation of the BRAF Mutation Assay
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Assessment method [10]
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Analytical and clinical validation of the companion diagnostic (cDx) assay was performed to determine the extent of agreement between the bioMerieux cDx assay (THxID BRAF Assay) and the Clinical Trial Assay (CTA) to detect BRAF mutations to determine participant eligibility into the study. Skin tissue samples collected at the Screening visit were used for this analysis. Multiple specimen per participant were analyzed.
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Timepoint [10]
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Screening
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Eligibility
Key inclusion criteria
- Adults at least 18 years of age
- Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF
mutation positive (V600E)
- Is treatment naive for advanced (unresectable) or metastatic melanoma, with the
exception of Interleukin 2 (IL-2) which is allowed.
- Has measurable disease according to RECIST 1.1 criteria.
- 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 adequate organ function.
- Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
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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
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy,
biologic therapy or surgery).
- Evidence of active central nervous system (CNS) disease.
- Previous treatment for metastatic melanoma, including treatment with BRAF or MEK
inhibitor.
- A history of other malignancy. Subjects who have been disease-free for 5 years or
subjects with a history of complete resected non-melanoma skin cancer or successfully
treated in situ carcinoma are eligible.
- History of Human Immunodeficiency Virus (HIV) infection.
- Certain cardiac abnormalities
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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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
Crossover
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Other design features
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Phase
Phase 3
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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
23/12/2010
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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
16/09/2016
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Sample size
Target
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Accrual to date
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Final
251
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
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Recruitment hospital [1]
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GSK Investigational Site - Westmead
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Recruitment hospital [2]
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GSK Investigational Site - Southport
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Recruitment hospital [3]
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GSK Investigational Site - Adelaide
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Recruitment hospital [4]
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GSK Investigational Site - Nedlands
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Recruitment postcode(s) [1]
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2145 - Westmead
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Recruitment postcode(s) [2]
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4215 - Southport
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Recruitment postcode(s) [3]
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5000 - Adelaide
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Recruitment postcode(s) [4]
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6009 - Nedlands
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Recruitment outside Australia
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United States of America
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Alabama
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United States of America
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California
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United States of America
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Florida
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United States of America
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Indiana
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United States of America
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Michigan
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United States of America
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New Hampshire
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United States of America
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New York
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Alberta
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Bordeaux
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France
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Lille
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France
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Marseille Cedex 5
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France
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Nice
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France
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Paris cedex 18
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France
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Paris
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France
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Reims
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France
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Villejuif
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Germany
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Baden-Wuerttemberg
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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Nordrhein-Westfalen
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Germany
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Rheinland-Pfalz
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Germany
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Saarland
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Germany
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Sachsen-Anhalt
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Germany
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Schleswig-Holstein
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Germany
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Thueringen
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Budapest
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Debrecen
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Gyor
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Miskolc
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Cork
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Italy
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Lazio
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Italy
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Liguria
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Italy
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Lombardia
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Italy
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Amsterdam
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Brzozow
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Konin
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Slupsk
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Warszawa
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
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Ryazan
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Russian Federation
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St. Petersburg
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Russian Federation
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Stavropol
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Hospitalet de Llobregat, Barcelona
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Sevilla
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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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Ethics approval
Ethics application status
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Summary
Brief summary
BRF113683 is a Phase III, randomized, open-label study comparing the efficacy, safety, and
tolerability of GSK2118436 to dacarbazine (DTIC), in subjects with BRAF mutant advanced
(Stage III) or metastatic (Stage IV) melanoma. Subjects will be randomized to receive 150 mg
of GSK2118436 twice daily or 1000 mg/m2 DTIC every 3 weeks and continue on treatment until
disease progression, death, or unacceptable adverse event. Subjects who progress on DTIC will
be allowed to crossover to an optional extension arm of the study to receive GSK2118436.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01227889
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Trial related presentations / publications
Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, Martin-Algarra S, Karaszewska B, Mauch C, Chiarion-Sileni V, Martin AM, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V, Chapman PB. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012 Jul 28;380(9839):358-65. doi: 10.1016/S0140-6736(12)60868-X. Epub 2012 Jun 25.
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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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Phone
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Fax
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Email
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Contact person for public queries
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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/NCT01227889
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