Prospective Translational Study Investigating Molecular Predictors of Resistance and Response to Regorafenib Monotherapy

Inclusion Criteria: 1. Patients with RAS mutant (MT) metastatic colorectal cancer (mCRC) who have been at least once treated with available therapies including fluoropyrimidine-based chemotherapy, oxaliplatin, irinotecan and an anti-angiogenic agent, except for patients who have not been treated with oxaliplatin due to previous documented peripheral neuropathy in an adjuvant setting or in those patients where disease has progressed within a short time from receiving adjuvant treatment (\<12 months). 2. Eligible to receive regorafenib within the context of PROSPECT-R trial at the Royal Marsden Hospital Exclusion criteria: A patient who meets any of the exclusion criteria will NOT be eligible for randomization. A patient must NOT 1. have had prior treatment with regorafenib or any other VEGF-targeting kinase inhibitor 2. have had previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors \[Ta (Noninvasive tumor), Tis (Carcinoma in situ) and T1 (Tumor invades lamina propria)\]. 3. Patients that are participating in another clinical trial involving an investigational medicinal product, unless it is more than 14 days after they have ceased the investigational medicinal product 4. Patients that are participating in another research study involving tumour tissue biopsies planned to take place during the time that the patient is participating in this study 5. Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment 6. If female and of childbearing potential, be engaged in breast feeding 7. Be unable to swallow oral tablets (crushing of study treatment tablets is not allowed) 8. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 month before the start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication) 9. Interstitial lung disease with ongoing signs and symptoms at the time of informed consent. 10. Ongoing infection \> Grade 2 NCI Common Toxicity Criterial for Adverse Effects (CTCAE). 11. Uncontrolled hypertension (Systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg) despite optimal medical management 12. Have congestive heart failure classified as New York Heart Association Class 2 or higher 13. Have had unstable angina (angina symptoms at rest) or new-onset angina \< 3 months prior to screening 14. Have had a myocardial infarction \< 6 months prior to initiation of study treatment