Efficacy and Safety Study of GSK1120212, a MEK Inhibitor, in Subjects With Uveal Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether GSK1120212, a MEK inhibitor, is an effective and safe treatment for cancer subjects with metastatic uveal melanoma and mutation-positive GNAQ or GNA11 metastatic melanoma.

Official Title
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A Single-Arm, Open-Label, Multi-Center Study to Investigate the Objective Response Rate, Safety, and Pharmacokinetics of GSK1120212, a MEK Inhibitor, in Subjects With Metastatic Uveal Melanoma or With Mutation-Positive GNAQ or GNA11 Metastatic Melanoma

Conditions
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GNA11 Mutation-positive Metastatic Melanoma, GNAQ Mutation-positive Metastatic Melanoma, Cancer, Metastatic Uveal Melanoma

Intervention / Treatment
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* Drug: GSK1120212


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of metastatic uveal melanoma or previously documented mutation-positive GNAQ or GNA11 metastatic melanoma not previously treated with a MEK inhibitor. Provide archival tumor tissue or, if tissue blocks are not available, undergo fresh tumor biopsy prior to enrollment. The patient has a radiographically measurable tumor. ECOG performance status 0, 1, or 2. The patient is able to swallow and retain oral medication. Life expectancy of at least 4 months. Toxicities from previous anti-cancer therapy (except alopecia) are recovered (Grade 1 or less) at the time of enrollment. The patient has adequate organ and bone marrow function. Sexually active patients must use medically acceptable methods of contraception during the course of the study. Female patients of childbearing potential must have a negative serum pregnancy test at screening. Exclusion Criteria: The patient has had any of the following within 21 days of starting study drug or anticipates the need for any of the following during the course of study treatment: chemotherapy, immunotherapy, biologic therapy, hormone therapy, major surgery, or tumor embolization. The patient has received experimental therapy within 21 days of starting study drug. The patient has received nitrosourea or mitomycin C within 42 days of starting study drug. The patient has received any herbal medications or palliative radiotherapy within 14 days of starting study drug. The patient is currently receiving anticoagulation therapy that is not well controlled. Ongoing or newly diagnosed eye abnormality other than symptoms due to uveal melanoma. History of retinal vein occlusion or central serous retinopathy. Current severe, uncontrolled systemic disease. History of leptomeningeal disease or spinal cord compression secondary to metastasis. Brain metastasis, unless previously treated with surgery, whole-brain radiation or stereotactic radiosurgery and the disease has been stable for at least 3 months without steroid use or on a stable dose of steroids for at least 1 month prior to starting study drug. Stability of brain metastases must be confirmed with imaging. The patient has a concurrent, active hematological malignancy or other solid tumor malignancy. History of clinically significant cardiac or pulmonary dysfunction. Allergy or hypersensitivity to components of the GSK1120212 formulation. The patient is pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: GSK1120212<br>* Repeating oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate as assessed by RECIST v1.1 |  | At least 12 weeks after initiating study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response, progression free survival, overall survival |  | Through study completion or early study discontinuation | 
| Safety, tolerability, and population pharmacokinetic parameters |  | Through study completion or early study discontinuation |