Safety, Tolerability and Efficacy of Regorafenib in Combination With FOLFIRINOX in Patients With Colorectal Cancer

Inclusion Criteria

• Written informed consent for full study.
• Documentation of tumor RAS mutation, wild-type homozygous, heterozygous status of UGT1A1 gene. The status of UGT1A1 gene will be performed by the laboratory chosen by the investigator
• Serum uracile 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
• 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 start of treatment.

8;Persistent proteinuria of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE V5) grade 3 (i.e. urinary protein ≥ 3.5 g/24 hrs) 9;Peripheral neuropathy > grade1 (NCI-CTCAE v5). 10.Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first dose of Treatment.

11.Ongoing infection >grade 2 (NCI-CTCAE v5). 12.Known history of human immunodeficiency virus (HIV) infection. 13.Chronic hepatitis B or C infection (if hepatitis status cannot be obtained from medical records, re-testing is required).

14.Seizure disorder requiring medication. 15.Symptomatic metastatic brain or meningeal tumors. 16.Evidence or history of any bleeding diathesis, irrespective of severity. Any hemorrhage or bleeding event ≥ grade 3 (NCI-CTCAE v5) within 4 weeks prior to the start of study medication.

17.History of organ allograft. 18.Non-healing wound, ulcer, or bone fracture. 19.Dehydration Grade 1 NCI-CTCAE v5). 20.Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.

21.Known hypersensitivity to any of the study drugs, study drug classes, or any constituent of the products.

22.Interstitial lung disease with ongoing signs and symptoms. 23.Concomitant intake of St. John's wort. 24.Live attenuated vaccines are prohibited 10 days before the treatment, during the treatment and 3 months after the termination of treatment 25.History of gastrointestinal fistula or perforation 26.Inability to swallow oral medication. 27.Any malabsorption condition. 28.Pregnant or breast-feeding subjects. 29.Any condition that, in the opinion of the investigator, would interfere with the evaluation of study treatment or interpretation of patient safety or study results.

30.Participation in another clinical study with an investigational product during the last 30 days before inclusion. 31.Patients who might be interconnected with or dependent on the sponsor site or the investigator.

32.Legal incapacity or limited legal capacity.