Fruquintinib Plus Capecitabine Versus Bevacizumab Plus Capecitabine as Maintenance Therapy Following First-line Treatment for Metastatic Colorectal Cancer

Inclusion Criteria: 1. 18-75 years old (including 18 and 75) at the time of signing the informed consent; 2. Patients who have been histologically or cytologically confirmed adenocarcinoma of the colon or rectum (stage IV); 3. Patients who have achieved disease control (including CR/PR and SD) after 4-6 months of first-line standard chemotherapy (FOLFOX, FOLFIRI, XELOX ± targeted therapy) and are progression free at the start of maintenance therapy; 4. At least one measurable metastatic lesion(s) as defined by RECIST version 1.1; 5. ECOG performance status of 0-1; 6. Body weight ≥40Kg; 7. LVEF≥50%; 8. Life expectancy≥3 months; 9. Adequate organ and bone marrow functions: Neutrophils \>1.5×109/L, platelets \>100×109/L, and hemoglobin \>9 g/dL; Total bilirubin \<1.5×upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) \<2.5×ULN (\<5×ULN in case of liver metastases); Creatinine clearance (calculated according to Cockcroft and Gault) ≥50 mL/min; Urinary protein / creatinine ratio \< 1 (or urine analysis \< 1 + or 24-hour urinary protein \< 1g / 24 h); 10. Able to take oral medication; 11. Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration; 12. 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; 3. Those who have been proved to be allergic to fruquintinib and / or its excipients; 4. Blood transfusion was performed within 1 week before randomization; 5. Non-controlled hypertension after monotherapy, that is, systolic blood pressure \> 140mmHg or diastolic blood pressure \> 90mmHg; 6. Intercurrence with one of the following: coronary artery disease, arrhythmia and heart failure; 7. Clinically significant electrolyte abnormality; 8. Proteinuria ≥ 2+ (1.0g/24hr); 9. Previous treatment with VEGFR inhibition; 10. Evidence of CNS metastasis; 11. Severe intolerance to capecitabine or 5-FU; 12. Disability of serious uncontrolled intercurrence infection; 13. Uncontrolled hemorrhage in GI; 14. Have evidence or a history of bleeding tendency within two months of the enrollment; 15. Abdominal fistula or gastrointestinal perforation occurred within 6 months before the first treatment, unless repaired by surgery; 16. Within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including stroke and transient ischemic attack) , etc.; 17. Within 6 months before the first recruitment occurs acute myocardial infarction, acute coronary syndrome or CABG; 18. Incomplete healing of skin trauma, surgical site, wound site or severe mucosal ulcer. Bone fracture or wounds that was not cured for a long time; 19. APTT and /or PT \>1.5×ULN; 20. Clinically detectable secondary primary malignancies at the time of enrollment, or had other malignancies in the past 5 years (excluding fully treated basal cell carcinoma of the skin or carcinoma in situ of the cervix); 21. Patients who are not suitable for the study judged by the researchers.