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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A | Experimental | Subjects who have had previous treatment with a BRAF inhibitor. |
|
| Cohort B | Experimental | Subjects who have had previous chemotherapy or immunotherapy without a BRAF inhibitor. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1120212 | Drug | Daily oral dosing |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Plasma Concentrations | Human plasma samples were analyzed for trametinib using a validated analytical method. | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Los Angeles | California | 90024 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23248257 | Result | 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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The study used a 2-stage, Green-Dahlberg design that permitted stopping the trial for futility if <3 objective responses were observed in the first 30 participants enrolled. If >=3 objective responses were observed, 55 participants could be enrolled in each cohort.
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| ID | Title | Description |
|---|---|---|
| FG000 | Trametinib 2 mg: Prior BRAF Inhibitors | Participants who were previously treated (before the start of this study) with BRAF inhibitors received trametinib (GSK1120212) 2 milligram (mg) tablets orally once daily (qd) until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, enrollment in this cohort was stopped because, after enrollment of the first 30 participants, no objective responses were observed. Eligible participants who had been consented at the time the 30th participant was dosed were allowed to enroll, leading to overenrollment of 10 participants (total of 40 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Week 8 |
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. |
| 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 | 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. | 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) | 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. | 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 | 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. | Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks) |
| 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. | Baseline (Day 1) until death due to any cause (up to 134 weeks) |
| 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. | Month 6, Month 12 and Month 24 |
| 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. | Baseline (Day 1) until tumor progression (up to approximately 57 weeks) |
| 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 |
| FG001 | Trametinib 2 mg: Prior Standard Therapy | Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Trametinib 2 mg: Prior BRAF Inhibitors | Participants who were previously treated (before the start of this study) with BRAF (v-Raf murine sarcoma viral oncogene homolog B1) inhibitors received trametinib 2 milligram (mg) tablets orally once daily (qd) until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, enrollment in this cohort was stopped because, after enrollment of the first 30 participants, no objective responses were observed. Eligible participants who had been consented at the time the 30th participant was dosed were allowed to enroll, leading to overenrollment of 10 participants (total of 40 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
| BG001 | Trametinib 2 mg: Prior Standard Therapy | Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All Treated Population: all participants who received at least one dose of investigational product | Posted | Number | Participants | 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) |
|
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| Primary | 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. | All Treated Population. A single participant could have been included in more than one subgroup. Subgroup analysis was not conducted in participants previously treated with BRAF inhibitors because there were no CRs or PRs among these participants. | Posted | Number | Participants | From Baseline (Day 1) until the time of the first documented evidence of a confirmed CR or PR (up to approximately 25 weeks) |
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| Primary | 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. | All Treated Population | Posted | Number | Participants | Week 8 |
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| Secondary | Mean Plasma Concentrations | Human plasma samples were analyzed for trametinib using a validated analytical method. | Pharmacokinetic (PK) Population: all participants in the All Treated Population for whom PK samples were obtained and analyzed. Only those participants available at the indicated time points were analyzed. | Posted | Mean | Standard Deviation | Nanograms (ng)/milliliter (mL) | 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 |
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| Secondary | 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. | All Treated Population | Posted | Number | Participants | From the date of the first dose of study medication until 28 days after the last dose (up to 477 days) |
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| Secondary | 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. | All Treated Population. Only those participants who had a confirmed CR or PR were analyzed for duration of response. | Posted | Median | 95% Confidence Interval | Months | 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) |
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| Secondary | 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. | All Treated Population | Posted | Median | 95% Confidence Interval | Months | Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks) |
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| Secondary | 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. | All Treated Population. A single participant could have been included in more than one subgroup. Subgroup analysis was not conducted in participants previously treated with BRAF inhibitors because this subgroup was stopped for futility and nearly all the participants progressed before 4 months. | Posted | Median | 95% Confidence Interval | Months | Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks) |
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| Secondary | 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. | All Treated Population | Posted | Median | 95% Confidence Interval | Months | Baseline (Day 1) until death due to any cause (up to 134 weeks) |
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| Secondary | 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. | All Treated Population | Posted | Number | Participants | Month 6, Month 12 and Month 24 |
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| Secondary | 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. | All Treated Population | Posted | Number | Participants | Baseline (Day 1) until tumor progression (up to approximately 57 weeks) |
|
Serious AEs and non-serious AEs are presented from the date of the first dose of study medication until the last participant's last visit (up to 1130 days).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Trametinib 2 mg: Prior BRAF Inhibitors | Participants who were previously treated (before the start of this study) with BRAF (v-Raf murine sarcoma viral oncogene homolog B1) inhibitors received trametinib 2 milligram (mg) tablets orally once daily (qd) until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, enrollment in this cohort was stopped because, after enrollment of the first 30 participants, no objective responses were observed. Eligible participants who had been consented at the time the 30th participant was dosed were allowed to enroll, leading to overenrollment of 10 participants (total of 40 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. | 4 | 40 | 37 | 40 | ||
| EG001 | Trametinib 2 mg: Prior Standard Therapy | Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. | 14 | 57 | 57 | 57 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Blood amylase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Cerebral hemorrhage | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gastrointestinal fistula | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastrointestinal hemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Hypoglycemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Pneumatosis | General disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Sepsis syndrome | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Tumor hemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Compression fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Skin erosion | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Hemorrhoids | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Systematic Assessment |
| |
| Edema peripheral | General disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Face edema | General disorders | MedDRA | Systematic Assessment |
| |
| Chills | General disorders | MedDRA | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA | Systematic Assessment |
| |
| Pain | General disorders | MedDRA | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Localized infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA | Systematic Assessment |
| |
| Hemoglobin decreased | Investigations | MedDRA | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA | Systematic Assessment |
| |
| Eye edema | Eye disorders | MedDRA | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Lymphedema | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Mood altered | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Breast enlargement | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA | Systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Sinus congestion | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C560077 | trametinib |
Not provided
Not provided
Not provided
| Male |
|
| White-White/Caucasian/European Heritage |
|
| OG001 | Participants Without Prior Brain Mets | Participants in this arm were those without prior brain metastasis, who were previoulsy treated with standard thearpy but not BRAF inhibitors. Participants received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. |
| OG002 | Participants With BRAF Mutation V600E | Participants in this arm were those with a positive BRAF mutation at V600E, who were previously treated with standard therapy but not with BRAF inhibitors. Participants received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. |
| OG003 | Participants With BRAF Mutation V600E and no Prior Brain Mets | Participants in this arm were those with a positive BRAF mutation at V600E but no prior brain metastasis, who were previously treated with standard therapy but not with BRAF inhibitors. Participants received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. |
| OG004 | Participants With BRAF Mutation V600K | Participants in this arm were those with a positive BRAF mutation at V600K, who were previously treated with standard therapy but not with BRAF inhibitors. Participants received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. |
|
|
|
| OG001 | Trametinib 2 mg: Prior Standard Therapy | Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
|
|
|
Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
|
|
| Trametinib 2 mg: Prior Standard Therapy |
Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
|
|
| OG001 | Trametinib 2 mg: Prior Standard Therapy | Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
|
|
| OG001 | Trametinib 2 mg: Prior Standard Therapy | Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
|
|
| OG001 | Participants Without Prior Brain Mets | Participants in this arm were those without prior brain metastasis who were previously treated with standard therapy but not with BRAF inhibitors. Participants received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. |
| OG002 | Participants With BRAF Mutation V600E | Participants in this arm were those with positive BRAF mutation at V600E, who were previously treated with standard therapy but not with BRAF inhibitors. Participants received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. |
| OG003 | Paticipants With BRAF Mutation V600E and no Prior Brain Mets | Participants in this arm were those with positive BRAF mutation at V600E but no prior brain metastasis, who were previously treated with standard therapy but not with BRAF inhibitors. Participants received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. |
| OG004 | Participants With BRAF Mutation V600K | Participants in this arm were those with positive BRAF mutation at V600K, who were previously treated with standard therapy but not with BRAF inhibitors. Participants received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. |
|
|
|
|
Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks.
|
|
| OG001 | Trametinib 2 mg: Prior Standard Therapy | Participants who were previously treated with standard therapy, but not with BRAF inhibitors, received trametinib 2 mg tablets orally qd until treatment discontinuation criteria were met. Per the pre-specified study design, enrollment could have been stopped if objective response was observed in fewer than 3 participants among the first 30 participants enrolled. Per this criterion, 55 participants were enrolled in this cohort because objective responses occurred in 6 participants at the time of the interim analysis. Eligible participants who had been consented at the time the 55th participant was dosed were allowed to enroll. This led to the overenrollment of 2 participants (total of 57 participants in this cohort). An interim analysis was performed after 30 participants had completed the first target post-dose disease assessment at 8 weeks. |
|
|