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

Brief Summary

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”

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.

  • Study Type: Interventional
  • Study Design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: July 2011

Interventions Used in this Clinical Trial

  • Drug: GSK1120212
    • Daily oral dosing

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: Cohort A
    • Subjects who have had previous treatment with a BRAF inhibitor.
  • Experimental: Cohort B
    • Subjects who have had previous chemotherapy or immunotherapy without a BRAF inhibitor.

Outcome Measures for this Clinical Trial

Primary 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)
      Safety Issue?: No
  • 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)
      Safety Issue?: No
  • Number of Participants With Best Unconfirmed Response at the Time of the Interim Analysis (Week 8)
    • Time Frame: Week 8
      Safety Issue?: No

Secondary 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
      Safety Issue?: No
  • 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)
      Safety Issue?: No
  • 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)
      Safety Issue?: No
  • 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)
      Safety Issue?: No
  • 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)
      Safety Issue?: No
  • Overall Survival
    • Time Frame: Baseline (Day 1) until death due to any cause (up to 134 weeks)
      Safety Issue?: No
  • Number of Participants Who Survived Until 6 Months, 12 Months and 24 Months From Baseline
    • Time Frame: Month 6, Month 12 and Month 24
      Safety Issue?: No
  • Number of Participants With Tumor Progression
    • Time Frame: Baseline (Day 1) until tumor progression (up to approximately 57 weeks)
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • GlaxoSmithKline
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • GSK Clinical Trials, Study Director, GlaxoSmithKline

Citations Reporting on Results

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.

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01037127