| Exclusion Criteria: | 1) Haematological malignancy associated with human immunodeficiency virus (HIV) infection or solid organ transplant.
2) Concurrent malignancy of solid tumors. Exception: Subjects who have been disease-free, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled. Consult GSK Medical Monitor if unsure whether second malignancies meet requirements specified above.
3) Currently receiving cancer therapy (chemotherapy, radiation therapy, immuno- therapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization). Note: For proliferative disease, hydroxyurea will be allowed during Week 1 and 2.
4) Received corticosteroids or imatinib within 24h of GSK1120212 administration.
5) Received gemtuzumab ozogamicin (myelotarg) within two weeks of GSK1120212 adminstration.
6) Received an investigational anti-cancer drug within four weeks or five half-lives, whichever is shorter of GSK1120212 administration--as long as a minimum of 14 days has passed between the last dose of the prior investigational anti-cancer drug and the first dose of GSK1120212.
7) Received major surgery, radiotherapy, or immunotherapy within four weeks of GSK1120212 administration.
8) Received chemotherapy regimens with delayed toxicity within the last four weeks (six weeks for prior nitrosourea or mitomycin C). Received chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last two weeks. Note: Use of hematopoetic growth factors is permitted at the discretion of the investigator according to published guidelines (e.g. NCCN, ASCO, ASH etc.).
9) Received a MEK inhibitor.
10) Current use of a prohibited medication or requires any of these medications during treatment with GSK1120212.
11) Current use of anticoagulants (e.g. warfarin, heparin) at therapeutic levels within seven days prior to the first dose of GSK1120212. Low dose (prophylactic) low molecular weight heparin (LMWH) is permitted provided that subject's PT and PTT meet entry criteria. Subjects requiring therapeutic levels of LMWH must receive approval from GSK Medical Monitor and be monitored appropriately as clinically indicated.
12) Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.
13) History of retinal vein occlusion (RVO), central serous retinopathy (CSR) or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, hypercholesterolemia, or history of hyperviscosity or hypercoagulability syndromes.)
14) Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as: *Evidence of new optic disc cupping; *Evidence of new visual field defects; *Intraocular pressure greater than 21 mm Hg.
15) Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
16) Concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol.
17) Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. *Subjects previously treated for these conditions that have had stable central nervous system (CNS) disease (verified with consecutive imaging studies) for greater than 3 months, are asymptomatic and off corticosteroids, or are on stable dose of corticosteroids for at least 1 month prior to study Day 1 are permitted. *Subjects are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs).
18) Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease).
19) Unresolved toxicity greater than common terminology criteria for adverse events (CTCAE) Grade 1 from previous anti-cancer therapy except alopecia (if applicable) unless agreed to by a GlaxoSmithKline (GSK) Medical Monitor and the investigator.
20) History or evidence of cardiovascular risk including any of the following: 1) QTcB greater than or equal to 480 msec; 2) history or evidence of current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for greater than 30 days prior to randomization are eligible; 3) history of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty or stenting within 6 months prior to randomization; 4) history or evidence of current greater than or equal to Class II congestive heart failure as defined by the New York Heart Association (NYHA); 5) treatment refractor hypertension defined as a blood pressure of systolic greater than 140 mmHg and/or diastolic greater than 90 mmHg which cannot be controlled by anti-hypertensive therapy; 6) patients with intra-cardiac defibrillators or permanent pacemakers; 7) cardiac metastases
21) Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, dimethyl sulfoxide (DMSO).
22) History of interstitial lung disease or pneumonitis.
23) Pregnant or lactating female.
24) Unwillingness or inability to follow the procedures outlined in the protocol. |