Fruquintinib Plus Capecitabine as Maintenance Treatment of RAS / BRAF Wild-type Metastatic Colorectal Cancer

Inclusion Criteria:

• Patients with histologically confirmed metastatic colorectal adenocarcinoma;
• 18-75 years old;
• Eastern Cooperation Oncology Group (ECOG) performance score 0-1;
• At least one evaluable lesion for disease assessment according to RECIST version 1.1;
• Able to take oral medications;
• Patient have achieved CR, PR or SD after up to 8 cycles of first-line standard FOLFOX / - FOLFIRI / XELOX / xeliri + cetuximab treatment, and remained unresectable;
• If radiotherapy has been performed before enrollment, at least one lesion should belocated outside the radiation field;
• Adequate organ functions as assessed by the following laboratory requirements:Leukocytes≥3.0x10^9/L, absolute neutrophil count≥1.5x10^9/L, plateletcount≥100x10^9/L, hemoglobin≥9g/dL; serum bilirubin≤1.5x the upper limit ofnormal(ULN);Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤2.5xULN; serum creatinine≤1.5x ULN.
• An expected survival of at least 12 weeks;
• Fertile male or female patients volunteered to use effective contraceptive methodsduring the study period and within 6 months after the end of treatment;
• Willing to provide written informed consent to study procedures.

Exclusion Criteria:

• Patients who have received fruquintinib;
• Patients who have received TACE within 6 weeks before enrollment;
• Participated in other unapproved or unlisted drug clinical trials in China within 4weeks before enrollment, and received corresponding experimental drug treatment;
• Patients with dysphagia, active peptic ulcer, intestinal obstruction, activegastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolledintestinal inflammatory diseases;
• International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN；
• The researchers judged clinically significant electrolyte abnormalities;
• At present, the patient has hypertension that cannot be controlled by drugs, which isspecified as: systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg;
• Patients currently have poorly controlled diabetes (fasting glucose level is greaterthan CTCAE grade 2 after regular treatment);
• Have received any surgery or invasive treatment or operation within 4 weeks beforeenrollment (except venous catheterization, puncture and drainage, etc.);
• Active or uncontrolled severe infection ≥ grade 2 according to National CancerInstitute Common Toxicity (NCI-CTC) criteria;
• Uncontrolled central nervous system metastasis or previous brain metastasis;
• Other malignant tumors in the past 5 years, except for skin basal cell or squamouscell carcinoma after radical surgery, or cervical carcinoma in situ;
• Any kind of concurrent cardiac disease with clinical meanings, such as cardiovascularaccident, myocardial infarction, thromboembolism or hemorrhage within 6 months beforeenrollment, congestive heart failure ≤New York Heart Association (NYHA) class 2;ventricular arrhythmias requiring drug treatment; LVEF < 50%;
• With positive urine protein and 24-hour urinary protein content>1g;
• Have a tendency of bleeding or clotting;
• Known human immunodeficiency virus (HIV) infection; known history of clinicallysignificant liver disease, including viral hepatitis;
• The target lesions have received brachytherapy (radioactive particle implantation)within 60 days before admission;
• Unrelieved toxic reactions higher than CTCAE V5.0 grade 1 caused by any previousanti-cancer treatment, excluding hair loss, lymphopenia and neurotoxicity ≤ grade 2caused by oxaliplatin;
• With any illness or medical conditions that may jeopardize the patient's compliance orinterfere the analyses or judgements of study results;
• Pregnancy or lactation at the time of study entry;
• With fertility but refuse to contraception.