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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Cancer; Metastatic Uveal Melanoma; GNA11 Mutation-positive Metastatic Melanoma; GNAQ Mutation-positive Metastatic Melanoma
• Intervention / Treatment: Drug: GSK1120212

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: GSK1120212; Repeating oral dose

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Anticipated): August 1, 2011
• Study Completion (Anticipated): May 1, 2012

Study Registration Dates

• First Submitted: March 18, 2010
• First Submitted That Met QC Criteria: March 31, 2011
• First Posted (Estimate): April 4, 2011

Study Record Updates

• Last Update Posted (Actual): December 12, 2017
• Last Update Submitted That Met QC Criteria: December 8, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uveal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Melanoma; Uveal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Trametinib
• Other Study ID Numbers: 114091