A Study to Look at the Electrical Activity of the Heart in Subjects With Solid Tumor Cancers, Before and After Receiving the Study Treatment, GSK1120212

Exclusion Criteria

• •History of prior exposure to a MEK(activated extracellular signal-regulated kinase) inhibitor or disease progression while receiving treatment with a MEK inhibitor.
• •Any of the following ECG findings: QTcF (preferred) or QTcB(interval corrected for heart rate by Bazett's formula) interval greater than and equal to 480 msec; PR(Partial response) interval greater than 220 msec or less than and equal to 110 msec; Bradycardia defined as sinus rate less than 50 beats per minute (bpm)
• •Cardiac conduction abnormalities denoted by any of the following: Evidence of second-degree (type II) or third-degree atrioventricular block; Evidence of ventricular pre-excitation; Electrocardiographic evidence of complete left bundle branch block (LBBB) NOTE: Right bundle branch block (RBBB), incomplete LBBB or incomplete RBBB will be exclusionary ONLY if QRS(a name for the combination of the graphical deflections seen on a typical electrocardiogram) duration is greater than 120 msec; Intraventricular conduction delay with QRS duration greater than 120 msec; Evidence of atrial fibrillation or history of atrial fibrillation within the past 6 months; Presence of cardiac pacemaker
• •History or evidence of any one of the following cardiovascular conditions within the past 6 months: Class II, III, IV heart failure as defined by the New York Heart Association; Cardiac angioplasty or stenting; Myocardial infarction; Unstable angina; Symptomatic peripheral vascular disease or other clinically significant cardiac disease; Cardiac metastases
• •Left ventricular ejection fraction (LVEF), as measured by ECHO or MUGA scan, below the institutional LLN, or if a LLN does not exist at an institution, less than 50%
• •Personal or family history of long-QT syndrome.
• •Treatment-refractory hypertension defined as a blood pressure of SBP (Systolic blood pressure) greater than 140 mmHg and/or DBP(Diastolic blood pressure) greater than 90 mmHg which cannot be controlled by anti-hypertensive therapy or lifestyle modifications.
• •Anti-cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) within 21 days prior to enrollment; chemotherapy regimens without delayed toxicity within 14 days prior to enrollment; or use of an investigational anti-cancer drug within 28 days preceding the first dose of study treatment. NOTE: Subjects with a history of prior anthracycline exposure are excluded.
• •Current use of a prohibited medication(s) or requires any of these medications during treatment with study treatment. NOTE: This includes medications that are listed as drugs that are generally accepted by the QTdrug.org (Advisory Board of the Arizona Center for Education and Research on Therapeutics to have a risk of causing Torsade de pointes (available at: http://www.azcert.org/medical-pros/drug-lists/bycategory.cfm).
• •Current use of therapeutic warfarin. NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted.
• •Any unresolved toxicity of greater than and equal to Grade 2, except alopecia or Grade 2 anemia, (NCI-CTCAE), version 4.0, from previous anti-cancer therapy.
• •Pre-existing Grade 2 or greater peripheral neuropathy.
• •History or current evidence/risk of RVO or CSR: History of RVO (Retinal vein occlusion) or CSR (Central serous retinopathy), or predisposing factors to RVO or CSR (i.e., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension or diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes); Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or CSR such as: Evidence of new optic disc cupping; Intraocular pressure \>21 mmHg as measured by tonography
• •History of interstitial lung disease or pneumonitis.
• •Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. NOTE: Subjects previously treated for these conditions that have had stable central nervous system disease (verified with consecutive imaging studies) for greater than 3 months, are asymptomatic and are not currently taking corticosteroids, or are on stable dose of corticosteroids for at least 30 days prior to Study Day 1 are permitted.
• •Presence of clinically significant gastrointestinal (GI) abnormalities that may affect the absorption of study treatment(s) including, but not limited to: Active, uncontrolled GI disease; Malabsorption syndrome; Substantial resection of the stomach, small bowel or colon. If clarification is needed as to whether a condition will significantly affect the absorption of study treatment(s), contact the GSK Medical Monitor.
• •History or presence of hepatic insufficiency (excluding metastatic hepatic carcinoma).
• •Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension), psychological,familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.
• •Lactating or actively breastfeeding females.
• •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to DMSO (Dimethyl Sulfoxide).