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

Inclusion criteria

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

Exclusion criteria

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