This is an exploratory biomarker study. Patients with metastatic colorectal cancer will receive regorafenib, which is FDA approved in this setting, on day 1-21 of every consecutive 28 day cycle. Patients will be asked to undergo tumor biopsy at baseline and 2 weeks after starting regorafenib. Peripheral blood samples will be collected at baseline 2 weeks after starting regorafenib, after initiation of cycle 3, and every 4 weeks thereafter.

Tumor tissue collected at baseline and 2 weeks after starting regorafenib will be analyzed for phosphoproteins and RNA. Peripheral blood samples will be collected and banked for protein, miRNA, and mutated DNA analysis.

Inclusion Criteria:

• Metastatic colorectal cancer suitable for regorafenib treatment
• Life expectancy of at least 12 weeks
• Able to understand and willing to sign written informed consent form
• Adequate bone marrow, liver, and renal function
• Glomerular filtration rate >/= 60 according to the Modified Diet in Renal Disease abbreviated formula
• Women of childbearing potential must have a negative serum pregnancy test
• Subject able to swallow and retain oral medication

Exclusion Criteria:

• Previous assignment to treatment in this study
• Uncontrolled hypertension
• Active or clinically significant cardiac disease
• Evidence or history of Bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding even Grade 3 or higher within 4 weeks prior to start of study medication
• Subjects with thrombotic, embolic, venous or arterial events
• Subjects with any previously untreated or concurrent cancer
• Pheochromocytoma
• Known history of human immunodeficiency virus infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
• Ongoing infection Grade 2 or higher
• Symptomatic metastatic brain or meningeal tumors
• Presence of a non-healing wound, non-healing ulcer, or bone fracture
• Renal failure requiring dialysis
• Dehydration Grade 1 or higher
• Seizure disorder requiring medication
• Persistent proteinuria Grade 3 or higher
• Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
• Pleural effusion or ascites that causes respiratory compromise
• History of organ allograft including corneal transplant
• Known or suspected allergy or hypersensitivity to the study drug
• Any malabsorption condition
• Women who are pregnancy or breast-feeding
• Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results
• Concurrent anticancer therapy
• Concurrent use of another investigational drug or device therapy during or within 4 weeks of trial entry
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
• Therapeutic anticoagulation with Vitamin-K antagonists or with heparins and heparinoids
• Use of any herbal remedy

Adverse events were collected for each subject from the time they signed the informed consent until study completion up to 1 year of treatment and safety follow-up. The period of collection depended on the length of the treatment period.