Study to Determine the Effectiveness of GSK1120212 in BRAF Mutation-positive Melanoma Previously Treated With or Without a BRAF Inhibitor

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01037127
First received: November 25, 2009
Last updated: February 13, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: GSK1120212
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 97
Study Start Date: November 2009
Study Completion Date: January 2013
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A
Subjects who have had previous treatment with a BRAF inhibitor.
Drug: GSK1120212
Daily oral dosing
Experimental: Cohort B
Subjects who have had previous chemotherapy or immunotherapy without a BRAF inhibitor.
Drug: GSK1120212
Daily oral dosing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01037127

Locations
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90024
United States, Colorado
GSK Investigational Site
Aurora, Colorado, United States, 80045
United States, New York
GSK Investigational Site
New York, New York, United States, 10016
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37232-6307
GSK Investigational Site
Nashville, Tennessee, United States, 37203
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030-4009
Australia, New South Wales
GSK Investigational Site
Westmead, New South Wales, Australia, 2145
Australia, Victoria
GSK Investigational Site
East Melbourne, Victoria, Australia, 3002
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01037127     History of Changes
Other Study ID Numbers: 113583
Study First Received: November 25, 2009
Results First Received: June 12, 2013
Last Updated: February 13, 2014
Health Authority: United States: Food and Drug Administration
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
GSK1120212
BRAF Inhibitor
melanoma
MEK Inhibitor

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Trametinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014