Efficacy of Modified Fruquintinib in Colorectal Cancer Liver Metastases: A Phase II Study

Inclusion Criteria:

1. . The pathological diagnosis was colorectal adenocarcinoma liver metastasis；
2. . Age: 18 to 75 years old,allgenders；
3. . Patients who have previously received first-line chemotherapy and have achieveddisease control (PR+SD) according to RECIST 1.1;
4. . Patients with liver metastasis of colorectal cancer who have undergone curativelocal treatment (surgery, ablation, SBRT) and achieved no evidence of disease (NED).Definition of NED: a. After local treatment, no residual signs of primary ormetastatic tumors are observed on CT, MRI, PET-CT imaging, or b. No cancer cells arefound in biopsies of suspicious lesions；
5. .Completed adjuvant chemotherapy after achieving NED (e.g. 4-8 cycles of CapOXregimen, 6-12 cycles of FOLFOX regimen, or without receiving adjuvant chemotherapyrecently) and evaluated as no disease progression. Last chemotherapy within 2 monthsfrom enrollment.
6. . The time interval between the last chemotherapy and enrollment does not exceed 2months;
7. . Performance status (ECOG score) ≤ 2
8. . Hematology: WBC > 3 × 10^9 / L; PLT > 80 × 10^9 / L; Hb > 90 g/L;
9. . Liver function: ALT and AST ≤ 2.5 × ULN; bilirubin ≤ 1.5 × ULN;
10. .Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCr) ≥ 60ml/min;
11. .Signed informed consent, willingness to undergo treatment according to this protocol,and good compliance with medication.

Exclusion Criteria:

1. .Patients with tumor progression before enrollment following the completion ofchemotherapy.
2. .Intestinal obstruction or incomplete intestinal obstruction.
3. .Co-existing with other serious illnesses, including severe electrolyte disorders,bleeding tendencies, etc.
4. .Active or uncontrolled severe infections: a) Known human immunodeficiency virus (HIV)infection. b) Known clinically significant liver disease history, including viralhepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBVinfection, i.e., HBV DNA positive (>1×104 copies/mL or >2000 IU/mL)]. c) Knownhepatitis C virus (HCV) infection with positive HCV RNA (>1×103 copies/mL), or otherhepatitis, liver cirrhosis.
5. .Women who are pregnant or breastfeeding and have childbearing potential but are nottaking adequate contraceptive measures.
6. .Patients with severe brain disorders or mental illnesses (such as depression, mania,obsessive-compulsive disorder, and schizophrenia) that affect the patient's ability toself-report.
7. .Patients with autoimmune diseases, blood system disorders, and a history of organtransplantation, long-term use of steroids, or immunosuppressive agents.
8. .History of other malignant tumors within the past 5 years, excluding cured cervicalcarcinoma in situ or basal cell carcinoma of the skin.
9. .History of organ transplantation (including autologous bone marrow transplantationand peripheral stem cell transplantation).
10. .Known or suspected allergies to the investigational drug fruquintinib.
11. .Hypertension that cannot be well controlled with antihypertensive medications (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
12. .Active cardiac disease within 6 months prior to treatment, including myocardialinfarction, severe/unstable angina pectoris. Left ventricular ejection fraction <50%on echocardiography, poorly controlled arrhythmias.
13. .Urinalysis indicating urine protein ≥2+ and 24-hour urine protein quantification >1.0g.