MEK Inhibitor MEK162 in Combination With Leucovorin Calcium, Fluorouracil, and Oxaliplatin in Treating Patients With Advanced Metastatic Colorectal Cancer

Exclusion Criteria

• •History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
• •Patients who have had chemotherapy, biologic, targeted, or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from grade 2 and above adverse events due to agents administered more than 4 weeks earlier (with the exception of alopecia or neuropathy)
• •History of retinal degenerative disease
• •History of Gilbert's syndrome
• •Previous or concurrent malignancy with the following exceptions:
• •* Adequately treated skin basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
• •* In situ carcinoma of the cervix, treated curatively and without evidence of recurrence
• •* A primary malignancy which has been completely resected and in complete remission for \>= 1 years
• •Prior therapy with a MEK- inhibitor
• •History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting \[CABG\], coronary angioplasty, or stenting) \< 6 months prior to screening
• •Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities \< 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia
• •Uncontrolled arterial hypertension despite appropriate medical therapy (defined as systolic blood pressure \> 160 or diastolic blood pressure \> 100)
• •Known positive serology for human immunodeficiency virus (HIV), active hepatitis B, and/or active hepatitis C infection
• •Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• •Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; NB: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment
• •Impairment of gastrointestinal function or gastrointestinal disease (e.g., active ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
• •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
• •Patients who have undergone major surgery =\< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
• •Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test
• •Women of child-bearing potential unless they are using highly effective methods of contraception throughout the study and for 60 days after study drug discontinuation
• •Sexually active males unless they use a condom during intercourse while taking the drug and for 60 days after stopping treatment and should not father a child in this period; a condom is required to be used also by vasectomized men
• •Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study
• •Current grade 3 or higher neuropathy
• •Use of other investigational drugs
• •Known hypersensitivity to any components of the study drugs
• •Prior intolerance to fluorouracil (5-FU) or oxaliplatin, excluding severe neuropathy that reversed to grade 2 or less