Clinical trial NCT01037127: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Keywords: GSK1120212
BRAF Inhibitor
melanoma
MEK Inhibitor
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-12-21
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Best Confirmed Response
timeFrame: 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)
measure: Number of Participants With Best Confirmed Response in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors
timeFrame: From Baseline (Day 1) until the time of the first documented evidence of a confirmed CR or PR (up to approximately 25 weeks)
measure: Number of Participants With Best Unconfirmed Response at the Time of the Interim Analysis (Week 8)
timeFrame: Week 8
Secondary outcomes:
measure: Mean Plasma Concentrations
timeFrame: 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
measure: Number of Participants With Any Adverse Event (AE)
timeFrame: From the date of the first dose of study medication until 28 days after the last dose (up to 477 days)
measure: Duration of Tumor Response
timeFrame: 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)
measure: Progression-free Survival (PFS)
timeFrame: Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks)
measure: PFS in the Indicated Subgroups of Participants Previously Treated With Standard Therapy But Not BRAF Inhibitors
timeFrame: Baseline (Day 1) until the time of disease progression or death due to any cause (up to approximately 57 weeks)
measure: Overall Survival
timeFrame: Baseline (Day 1) until death due to any cause (up to 134 weeks)
measure: Number of Participants Who Survived Until 6 Months, 12 Months and 24 Months From Baseline
timeFrame: Month 6, Month 12 and Month 24
measure: Number of Participants With Tumor Progression
timeFrame: Baseline (Day 1) until tumor progression (up to approximately 57 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Aurora
country: United States
facility: GSK Investigational Site
state: Colorado
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Westmead
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: East Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
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.