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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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ClinicalTrials.gov Identifier: NCT01037127
Recruitment Status : Completed
First Posted : December 21, 2009
Results First Posted : March 31, 2014
Last Update Posted : March 31, 2014
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE November 25, 2009
First Posted Date  ICMJE December 21, 2009
Results First Submitted Date  ICMJE June 12, 2013
Results First Posted Date  ICMJE March 31, 2014
Last Update Posted Date March 31, 2014
Study Start Date  ICMJE November 2009
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2014)
  • Number of Participants With Best Confirmed Response [ 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) ]
    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 [ 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) ]
    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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2009)
Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2014)
  • Mean Plasma Concentrations [ 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 ]
    Human plasma samples were analyzed for trametinib using a validated analytical method.
  • Number of Participants With Any Adverse Event (AE) [ Time Frame: From the date of the first dose of study medication until 28 days after the last dose (up to 477 days) ]
    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 [ 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) ]
    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) [ Time Frame: Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks) ]
    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 [ Time Frame: Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks) ]
    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 [ Time Frame: Baseline (Day 1) until death due to any cause (up to 134 weeks) ]
    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 [ Time Frame: Month 6, Month 12 and Month 24 ]
    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 [ Time Frame: Baseline (Day 1) until tumor progression (up to approximately 57 weeks) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2009)
  • AEs and changes in laboratory values and vital signs. [ Time Frame: 6 months ]
  • Duration of response. [ Time Frame: 6 months ]
  • GSK1120212 trough concentrations and population PK parameters (as data permit). [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE Drug: GSK1120212
Daily oral dosing
Study Arms  ICMJE
  • Experimental: Cohort A
    Subjects who have had previous treatment with a BRAF inhibitor.
    Intervention: Drug: GSK1120212
  • Experimental: Cohort B
    Subjects who have had previous chemotherapy or immunotherapy without a BRAF inhibitor.
    Intervention: Drug: GSK1120212
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 22, 2011)
97
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2009)
55
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01037127
Other Study ID Numbers  ICMJE 113583
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP