['metastatic colorectal cancer']
['regorafenib']

        Inclusion Criteria:

          1. Signed and dated informed consent.

          2. Patients with histologically proven metastatic colorectal cancer

          3. Patients previously treated with, or who are not considered candidates for available
             therapies, i.e., fluoropyrimidine-based chemotherapy, anti-VEGF therapy and anti-EGFR
             therapy (if patients were RAS wild-type).

          4. ECOG PS = 0 or 1

          5. Aged 18-years or older

          6. Life expectancy of at least 3 months

          7. Adequate renal, bone marrow, liver and pancreatic functions:

               -  Estimated creatinine clearance ≥ 30 mL/min as calculated using the
                  Cockcroft-Gault equation

               -  Platelet count ≥ 100.000/mm3; hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥
                  1500/mm3. Transfusion to meet the inclusion criteria will not be allowed

               -  Total bilirubin ≤ 1.5 the upper limit of normal value (ULN); alanine
                  aminotransferase (ALAT) and aspartame aminotransferase (ASAT) ≤ 3.0 x ULN (≤ 5.0
                  x ULN for patients with liver involvement of their cancer); alkaline phosphatase
                  (ALP) ≤ 2.5 x ULN (≤ 5.0 x ULN for patients with liver involvement of their
                  cancer and/or have bone metastases)

          8. International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT)
             or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment
             with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g.,
             heparin, will be allowed to participate provided no prior evidence of an underlying
             abnormality in these parameters exists. Close monitoring of at least weekly evaluation
             will be performed until INR and PTT are stable based on a pre-dose measurement as
             defined by the local standard of care

          9. At least one target lesion on CT scan

         10. No contraindication to Iodine contrast media injection during CT.

         11. For women of childbearing potential, blood or urine pregnancy test performed a maximum
             of 7 days before start of study treatment and negative result documented before start
             of study treatment

         12. When applicable, i.e., women of childbearing potential having sexual activity, men
             having sexual activity, must agree to use an adequate contraception before entering
             the study, until at least 8 weeks after the last study drug administration

         13. Registration in a national health care system (CMU included).

        Exclusion Criteria:

          1. Any psychological, familial, sociological or geographical condition potentially
             hampering compliance with the study protocol and follow-up schedule; those conditions
             should be discussed with the patient before inclusion in the trial ; planned surgical
             procedure within the first month of treatment or any procedure that might change the
             timing of regorafenib administration during the first month of treatment

          2. Patients under judicial protection (curatorship, tutorship) and/or deprived of freedom

          3. Major surgical procedure, open biopsy or significant traumatic injury within 28 days
             before start of study medication

          4. Pregnancy or breastfeeding

          5. Congestive heart failure ≥ New York Heart Association (NYHA) class 2

          6. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
             months)

          7. Myocardial infarction less than 6 months before the start of study medication

          8. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are
             permitted)

          9. Uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic pressure >90
             mmHg despite optimal medical management)

         10. Arterial or venous thrombotic or embolic events such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
             within 6 months 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

         11. Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2,
             NCI-CTCAE v 4.0 dyspnea)

         12. Ongoing infection >grade 2, NCI- CTCAE v 4.0

         13. Previous or concurrent cancer that is distinct in primary site or histology from
             colorectal cancer within 5 years prior to inclusion, except for curatively treated
             cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta
             [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria])

         14. Known history of human immunodeficiency virus (HIV) infection

         15. Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral
             therapy

         16. Patients with seizure disorder requiring medication

         17. History of organ allograft

         18. Patients with evidence or history of any bleeding diathesis, irrespective of severity

         19. Any hemorrhage or bleeding event ≥ Grade 3, NCI-CTCAE v 4.0 within 4 weeks prior to
             the start of study medication

         20. Non-healing wound, non-healing ulcer or non-healing bone fracture

         21. Dehydration grade ≥1, NCI-CTCAE v 4.0

         22. Known hypersensitivity to the study drug, study drug classes or excipient in the
             formulation

         23. Interstitial lung disease with ongoing signs or symptoms at the time of inclusion

         24. Persistent proteinuria >3.5 g/24 hour measured by urine protein-creatinine ratio from
             a random urine sample (≥ Grade 3, NCI-CTCAE v 4.0)

         25. Patients unable to swallow oral medication

         26. Any malabsorption condition

         27. Unresolved toxicity higher than Grade 1, NCI-CTCAE v 4.0, attributed to any prior
             therapy/procedure excluding alopecia and oxaliplatin induced neuropathy

         28. Systemic anticancer therapy including cytotoxic therapy, signal transduction
             inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks

         29. Treatment with any other investigational medicinal product within 28 days prior to
             study entry

         30. Chronic treatment potentially interacting with the study medication, i.e. strong
             CYP3A4 inducers/inhibitors, strong UGT1A9 inhibitors
      