Back to resultsStudy to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor
Primary Purpose
Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GSK1120212
Sponsored by
About this trial
This is an interventional treatment trial for Cancer focused on measuring GSK1120212, BRAF Inhibitor, melanoma, MEK Inhibitor
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A
Cohort B
Arm Description
Subjects who have had previous treatment with a BRAF inhibitor.
Subjects who have had previous chemotherapy or immunotherapy without a BRAF inhibitor.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
Mean Plasma Concentrations
Human plasma samples were analyzed for trametinib using a validated analytical method.
Number of Participants With Any Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. AE and serious AE (SAE) data were collected from the start of the investigational product and continued until the End of Treatment Visit. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Duration of Tumor Response
Duration of tumor response is defined as the time from the first documented evidence of a CR or PR to disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause. No participants who were previously treated with BRAF inhibitors had 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; thus, no duration of response data can be presented.
Progression-free Survival (PFS)
PFS is defined as the interval between the treatment start date and the earliest date of disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause, whichever occurred first. Participants who had not progressed or died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
PFS in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors
PFS 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. Per RECIST version 1.1, PFS is defined as the interval between the treatment start date and the earliest date of disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause, whichever occurred earliest. Brain metastasis is a cancer that has spread to the brain from another location of the body.
Overall Survival
Overall survival is defined as the time from the treatment start date until death due to any cause. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Number of Participants Who Survived Until 6 Months, 12 Months and 24 Months From Baseline
Overall survival (defined as the time from the treatment start date until death due to any cause) data data are presented as the number of participants who were alive 6 months, 12 months and 24 months after Baseline. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Number of Participants With Tumor Progression
Tumor progression was assessed as disease progression (DP), defined as at least a 20 percent increase in the sum of diameters of target lesions (representative of all involved organs), taking as reference the smallest sum on study; unequivocal progression of non-target lesions; or the appearance of a new lesion. Because melanoma often progresses to the brain/central nervous system (CNS) and this study enrolled approximately 20% participants with prior brain metastases, tumor progression in the brain/CNS was summarized. Paticipants could have been included in more than one category.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01037127
Brief Title
Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
January 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer
Keywords
GSK1120212, BRAF Inhibitor, melanoma, MEK Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
97 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A
Arm Type
Experimental
Arm Description
Subjects who have had previous treatment with a BRAF inhibitor.
Arm Title
Cohort B
Arm Type
Experimental
Arm Description
Subjects who have had previous chemotherapy or immunotherapy without a BRAF inhibitor.
Intervention Type
Drug
Intervention Name(s)
GSK1120212
Intervention Description
Daily oral dosing
Primary Outcome Measure Information:
Title
Number of Participants With Best Confirmed Response
Description
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.
Time Frame
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)
Title
Number of Participants With Best Confirmed Response in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors
Description
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.
Time Frame
From Baseline (Day 1) until the time of the first documented evidence of a confirmed CR or PR (up to approximately 25 weeks)
Title
Number of Participants With Best Unconfirmed Response at the Time of the Interim Analysis (Week 8)
Description
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.
Time Frame
Week 8
Secondary Outcome Measure Information:
Title
Mean Plasma Concentrations
Description
Human plasma samples were analyzed for trametinib using a validated analytical method.
Time Frame
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
Title
Number of Participants With Any Adverse Event (AE)
Description
An AE is defined as any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. AE and serious AE (SAE) data were collected from the start of the investigational product and continued until the End of Treatment Visit. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.
Time Frame
From the date of the first dose of study medication until 28 days after the last dose (up to 477 days)
Title
Duration of Tumor Response
Description
Duration of tumor response is defined as the time from the first documented evidence of a CR or PR to disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause. No participants who were previously treated with BRAF inhibitors had 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; thus, no duration of response data can be presented.
Time Frame
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)
Title
Progression-free Survival (PFS)
Description
PFS is defined as the interval between the treatment start date and the earliest date of disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause, whichever occurred first. Participants who had not progressed or died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Time Frame
Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks)
Title
PFS in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors
Description
PFS 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. Per RECIST version 1.1, PFS is defined as the interval between the treatment start date and the earliest date of disease progression (at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; unequivocal progression of non-target lesions, or the appearance of a new lesion) or death due to any cause, whichever occurred earliest. Brain metastasis is a cancer that has spread to the brain from another location of the body.
Time Frame
Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks)
Title
Overall Survival
Description
Overall survival is defined as the time from the treatment start date until death due to any cause. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Time Frame
Baseline (Day 1) until death due to any cause (up to 134 weeks)
Title
Number of Participants Who Survived Until 6 Months, 12 Months and 24 Months From Baseline
Description
Overall survival (defined as the time from the treatment start date until death due to any cause) data data are presented as the number of participants who were alive 6 months, 12 months and 24 months after Baseline. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off.
Time Frame
Month 6, Month 12 and Month 24
Title
Number of Participants With Tumor Progression
Description
Tumor progression was assessed as disease progression (DP), defined as at least a 20 percent increase in the sum of diameters of target lesions (representative of all involved organs), taking as reference the smallest sum on study; unequivocal progression of non-target lesions; or the appearance of a new lesion. Because melanoma often progresses to the brain/central nervous system (CNS) and this study enrolled approximately 20% participants with prior brain metastases, tumor progression in the brain/CNS was summarized. Paticipants could have been included in more than one category.
Time Frame
Baseline (Day 1) until tumor progression (up to approximately 57 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
GSK Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
GSK Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
GSK Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
GSK Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6307
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
GSK Investigational Site
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
GSK Investigational Site
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
GSK Investigational Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
12. IPD Sharing Statement
Citations:
PubMed Identifier
23248257
Citation
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.
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Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor
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