Evaluation of Treatment Response With CHOI and RECIST Criteria and CT Texture Analysis in Patients With Metastatic Colorectal Cancer Treated With Regorafenib

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

What this study is about