Fruquintinib Combined With TAS-102 in the Treatment of Patients With Advanced Metastatic CRC

Inclusion Criteria: 1. ≥ 18 and ≤ 75 years of age; 2. Histological or cytological confirmed advanced metastatic colorectal cancer; 3. Refractory to at least second line standard treatment containing fluorouracil, oxaliplatin and irinotecan; 4. At least one measurable lesion (larger than 10 mm in diameter by spiral CT scan or 20mm by conventional CT scan); 5. ECOG performance status of 0-1; 6. Life expectancy ≥ 12 weeks; 7. No previous treatment with vascular endothelial growth factor receptor (VEGFR) inhibitor (TKI); 8. Signed and dated informed consent; 9. Adequate hepatic, renal, heart, and hematologic functions; 10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure. Exclusion Criteria: 1. Pregnant or lactating women; 2. Any factors that influence the usage of oral administration or any disease or condition that affects drug absorption; 3. Previous treatment with TAS-102; 4. Participated in clinical trials of other drugs within four weeks before enrollment; 5. Received other systemic anti-tumor therapy within 4 weeks before enrollment, including chemotherapy, signal transduction inhibitors, hormone therapy and immunotherapy; 6. International normalized ratio (INR) \> 1.5 or partially activated prothrombin time (APTT) \> 1.5 × ULN; 7. Clinically significant electrolyte abnormalities; 8. Subjected with hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg; 9. Unrelieved toxic reactions higher than CTCAE V5.0 grade 1 caused by any previous anti-cancer treatment; 10. Incomplete healing of skin wound, surgical site, traumatic site, severe mucosal ulcer or fracture; 11. Conditions that may cause gastrointestinal bleeding and perforation determined by the researcher; 12. History of arterial thrombosis or deep venous thrombosis within 6 months before enrollment; 13. Stroke and / or transient cerebral ischemia occurred within 12 months before enrollment; 14. Cardiovascular diseases with significant clinical significance; 15. LVEF\<50%; 16. Congestive heart failure New York Heart Association (NYHA) grade \> 2; 17. Evidence of CNS metastasis; 18. Previous treatment with VEGFR inhibition; 19. Ventricular arrhythmias requiring drug treatment; 20. Proteinuria ≥ 2+ (1.0g/24hr); 21. Coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy; 22. Other malignant tumors in the past 5 years, except skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ; 23. Active infection that is not controlled clinically, such as acute pneumonia, active hepatitis B or hepatitis C; 24. By judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study.