Fruquintinib Combined With mFOLFOX6/FOLFIRI in First-line Treatment for Metastatic Colorectal Cancer

Inclusion Criteria:

1. Age ≥ 18 years, ≤75 years
2. Histologically confirmed unresectable or metastatic stage colorectal cancer
3. Known RAS activating mutation/wild type and BRAF wild type;
4. Patients have not received systematic treatment for unresectable or metastaticcolorectal cancer (those who have received adjuvant or neoadjuvant chemotherapy withone regimen and relapsed more than 12 months after the end of chemotherapy can beenrolled);
5. At least one measurable disease according to RECIST 1.1 guidelines for solid tumors；
6. BMI≥18；
7. ECOG 0-1
8. Life expectancy > 12 weeks
9. Patients must have adequate organ function
10. Women of childbearing age must have a negative pregnancy test within the first day ofthe study, and contraceptive methods should be taken during the study until 6 monthsafter the last administration;
11. Informed consent has been signed.

Exclusion Criteria:

1. Have received other systemic anti-tumor therapies within 2 weeks beforerecruited(eg.chemotherapy or radiotherapy, immunotherapy, biological or hormonaltherapy, or any VEGFR inhibitor treatment);
2. Known BRAF activating mutation
3. systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg regardless ofany antihypertensive drugs; Or patients need more than two antihypertensive drugs;
4. Clinically significant electrolyte abnormality;
5. Proteinuria ≥ 2+ (1.0g/24hr);
6. Patients have untreated central nervous system metastasis;
7. Patients have not recovered from all toxicities associated with prior anti-tumortherapy ,to acceptable baseline status, or a National Cancer Institute CommonTerminology Criteria for Adverse Events(NCI CTCAE v5.0) Grade of 0 or 1, except foralopecia and oxaliplatin induced neurotoxicity ≤ 2 , and the previous surgery did notrecover completely;
8. Have received other systemic anti-tumor therapies within 4 weeks before recruited;
9. Clinical uncontrolled active infections, such as acute pneumonia and active hepatitisB / C (previous history of hepatitis B virus infection, whether drug controlled ornot, HBV DNA ≥ 104) × Copy number or ≥ 2000 IU / ml);
10. Dysphagia or known malabsorption of drugs;
11. Active gastric and duodenal ulcer, ulcerative colitis or uncontrolled hemorrhage inGI;
12. Have evidence or history of bleeding tendency within 2 months after enrollment, theresearcher assessed that moderate or severe bleeding tendency was not suitable forenrollment;
13. Stroke (including transient ischemic attack) occurred within 12 months beforeadmission;
14. Patients had other malignant tumors in the past 5 years or at the same time (exceptfor the cured skin basal cell carcinoma and cervical carcinoma in situ);
15. Pregnant or lactating women;
16. Allergic to fruquintinib；
17. History of immunodeficiency, including HIV positive, other acquired or congenitalimmunodeficiency diseases, or organ transplantation;
18. Patients with acute myocardial infarction, severe / unstable angina pectoris orcoronary artery bypass grafting within 6 months before admission; Or a history ofarterial thrombosis or deep venous thrombosis;
19. There are concomitant diseases (such as severe hypertension, diabetes, thyroiddisease, active infection, etc.) that seriously endanger the safety of patients oraffect the completion of the study, or any laboratory abnormalities that are notsuitable for participating in the clinical trial according to the judgment of theresearcher,
20. Serious psychological or mental disorders that may affect the compliance study;
21. Participating in other drug clinical trials within 4 weeks before recruited.