Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor
An Open-Label, Multi-Center Study to Investigate the Objective Response Rate, Safety, and Pharmacokinetics of GSK1120212, a MEK Inhibitor, in BRAF Mutation-positive Melanoma Subjects Previously Treated With or Without a BRAF Inhibitor
1 other identifier
interventional
97
2 countries
10
Brief Summary
MEK113583 is a Phase II open-label, multi-site study to investigate the objective response rate, safety, and pharmacokinetics of GSK1120212 in subjects with BRAF mutation-positive melanoma who were previously treated with or without a BRAF inhibitor. GSK1120212 is a potent and highly selective inhibitor of MEK activation and kinase activity.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 cancer
Started Nov 2009
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2009
CompletedFirst Submitted
Initial submission to the registry
November 25, 2009
CompletedFirst Posted
Study publicly available on registry
December 21, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2013
CompletedResults Posted
Study results publicly available
March 31, 2014
CompletedMarch 31, 2014
January 1, 2014
1.7 years
November 25, 2009
June 12, 2013
February 13, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Number of Participants With Best Confirmed Response
Best confirmed response was assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Best response was measured either as a complete response (CR), defined as the disappearance of all target lesions and pathological lymph nodes \<10 millimeters (mm), or a partial response (PR), defined as at least a 30% decrease in the sum of the diameters of target lesions. To be assigned a status of confirmed CR or PR, a confirmatory disease assessment was required no less than 28 days after the criteria for response were first met.
From Baseline (Day 1) until the time of the first documented evidence of a confirmed complete response or partial response (up to approximately 25 weeks)
Number of Participants With Best Confirmed Response in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors
The number of participants with best confirmed response was analyzed for the following subgroups of participants previously treated with standard therapy but not BRAF inhibitors: (1) participants with prior (before the start of this study) brain metastases (mets); (2) participants without prior brain mets; (3) participants with BRAF mutation V600E; (4) participants with BRAF mutation V600E and no prior brain mets; and (5) participants with BRAF mutation V600K. Objective response was assessed per RECIST version 1.1. Objective response was measured either as CR, defined as the disappearance of all target lesions and pathological lymph nodes \<10 mm, or PR, defined as at least a 30% decrease in the sum of the diameters of target lesions. To be assigned a status of confirmed CR or PR, a confirmatory disease assessment was required no less than 28 days after the criteria for response were first met. Brain metastasis is a cancer that has spread to the brain from another location of the body.
From Baseline (Day 1) until the time of the first documented evidence of a confirmed CR or PR (up to approximately 25 weeks)
Number of Participants With Best Unconfirmed Response at the Time of the Interim Analysis (Week 8)
An interim analysis was performed using data collected approximately 12 and 13 weeks after the 30th participant was enrolled in the prior BRAF inhibitor and prior standard therapy groups, respectively. The best unconfirmed response by the investigator per RECIST version 1.1 was assessed. The study design permitted stopping the study for futility if \<3 best confirmed responses were observed in the first 30 participants of each treatment arm after completing the first post-dose assessment at Week 8. Best response was measured as either a CR, defined as the disappearance of all target lesions and pathological lymph nodes \<10 millimeters, or a PR, defined as at least a 30% decrease in the sum of the diameters of target lesions.
Week 8
Secondary Outcomes (8)
Mean Plasma Concentrations
Day 15, pre-dose, 0.5-2 hours (hrs) post-dose, 2-4 hrs post-dose, and 4-8 hrs post-dose; Week 4, pre-dose; Week 8, pre-dose; Week 12, pre-dose
Number of Participants With Any Adverse Event (AE)
From the date of the first dose of study medication until 28 days after the last dose (up to 477 days)
Duration of Tumor Response
From the time of the first documented evidence of a confirmed CR or PR until disease progression or death due to any cause (up to approximately 40 weeks)
Progression-free Survival (PFS)
Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks)
PFS in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors
Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks)
- +3 more secondary outcomes
Study Arms (2)
Cohort A
EXPERIMENTALSubjects who have had previous treatment with a BRAF inhibitor.
Cohort B
EXPERIMENTALSubjects who have had previous chemotherapy or immunotherapy without a BRAF inhibitor.
Interventions
Eligibility Criteria
You may qualify if:
- Metastatic cutaneous melanoma that was previously treated with: (Cohort A) a BRAF inhibitor either with or without other prior therapy. (Cohort B) at least 1 prior chemotherapy or immunotherapy, without treatment with a BRAF inhibitor.
- Documented positive BRAF mutation (V600E, V600K, or V600D).
- Subjects must provide archived tumor tissue or undergo fresh tumor biopsy prior to enrollment.
- The subject must have a radiographically measurable tumor.
- The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
- Able to swallow and retain oral medication.
- Sexually active subjects must use acceptable methods of contraception during the course of the study.
- Adequate organ system function and blood cell counts.
You may not qualify if:
- The subject has had major surgery or received certain types of cancer therapy within 21 days before starting the study.
- Previous treatment with a MEK inhibitor.
- Current use of a prohibited medication listed in the protocol.
- Uncontrolled glaucoma.
- Brain metastasis, unless previously treated with surgery or stereotactic radiosurgery, and the disease has been stable for at least 2 months prior to enrollment.
- Current severe or uncontrolled systemic disease.
- History of clinically significant heart, lung, or eye/vision problems.
- Significant unresolved side effects from previous anti-cancer therapy.
- The subject is pregnant or breastfeeding.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (10)
GSK Investigational Site
Los Angeles, California, 90024, United States
GSK Investigational Site
Aurora, Colorado, 80045, United States
GSK Investigational Site
New York, New York, 10016, United States
GSK Investigational Site
Philadelphia, Pennsylvania, 19104, United States
GSK Investigational Site
Nashville, Tennessee, 37203, United States
GSK Investigational Site
Nashville, Tennessee, 37232-6307, United States
GSK Investigational Site
Houston, Texas, 77030-4009, United States
GSK Investigational Site
Westmead, New South Wales, 2145, Australia
GSK Investigational Site
East Melbourne, Victoria, 3002, Australia
GSK Investigational Site
Nedlands, Western Australia, 6009, Australia
Related Publications (1)
Kim KB, Kefford R, Pavlick AC, Infante JR, Ribas A, Sosman JA, Fecher LA, Millward M, McArthur GA, Hwu P, Gonzalez R, Ott PA, Long GV, Gardner OS, Ouellet D, Xu Y, DeMarini DJ, Le NT, Patel K, Lewis KD. Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J Clin Oncol. 2013 Feb 1;31(4):482-9. doi: 10.1200/JCO.2012.43.5966. Epub 2012 Dec 17.
PMID: 23248257RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 25, 2009
First Posted
December 21, 2009
Study Start
November 1, 2009
Primary Completion
July 1, 2011
Study Completion
January 1, 2013
Last Updated
March 31, 2014
Results First Posted
March 31, 2014
Record last verified: 2014-01