| Exclusion Criteria: | 1) Previous therapy with the following molecularly-targeted agents: (1) MEK inhibitors (such as PD0325901); (2) VEGF or VEGFR inhibitors (such as Avastin and small molecule inhibitors with activity against any of the VEGF receptor isoforms); (3) Raf inhibitors (such as sorafenib)
2) Patients with a history of primary central nervous system tumors or brain metastases or who have singns/symptoms attributable to brain metastases and have not been assessed wtih radiologic imaging to rule out the presence of brain metastases.
3) Clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or IV), arrhythmia or conduction abnormality requiring medication, or cardiomyopathy; or clinically uncontrolled hypertension (Blood pressure > 160/110 mmHg). Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: 1). LVEF < 45% as determined by MUGA scan or echocardiogram 2) Complete left bundle branch block 3) Obligate use of cardiac pacemaker 4). Congenital long QT syndrome 5) History or presence of ventricular tachyarrhythmia.
4) (Cont'd from #3) - Presence of unstable atrial fibrillation (ventricular resonse > 100 bpm). Patients with stable atrial fibrillation are eligible, provided they do not meet any of the other exclusion criteria. 7) Clinically significant resting bradycardia (<50 bmp) 8) QTc > 480 msec on screening ECG 9) Right bundle branch block + left anterior hemiblock (bifasicular block) 10) Angina pectoria </= 3 months prior to starting study drug. 11) Acute MI </= 3 months prior to starting study drug.
5) Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
6) Active, and uncontrolled clinically significant infection.
7) Breastfeeding women.
8) Chronic anticoagulation therapy with full strength acetylsalicylic acid (ASA), warfarin sodium, or heparin (low dose ASA </= 100 mg, or low dose warfarin </= 1 mg to maintain indwelling venous access device patency is allowed).
9) History of thromboembolic or cerebrovascular events within the last 12 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism.
10) History of melena, hematemesis, or hemoptysis within the last 3 months.
11) Prior acute or chronic pancreatitis of any etiology.
12) Prior intra or extrahepatic biliary obstruction within the previous 12 months, or history of malignant obstruction requiring a biliary stent, unless stably treated with no prior obstruction or blockage of the stent.
13) Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for the study.
14) Blood pressure > 140/90.
15) Current evidence of retinal disease, confirmed by ophthalmologic examination |