Efficacy and Safety of Trifluridine/Tipiracil Combined With Fufuquitinib for Third-line Treatment of mCRC

Inclusion criteria

• 1.Age 18-75 (at the time of signing the informed consent);ECOG PS score: 0-1; Expected survival time > 3 months.

2.Patients with advanced colorectal adenocarcinoma confirmed by histopathology who had failed standard first - and second-line treatment.

3.At least 1 measurable lesion was present according to RECIST1.1 criteria. 4.Good organ function, laboratory tests meet the following criteria:

• Hemoglobin ≥90g/L;Absolute count of neutrophils (ANC) ≥1.5×109/L;Platelet ≥100×109/L;
• ALT and AST≤2.5 upper limit of normal (ULN).ALP≤2.5 ULN;(if liver metastases ≤5 ULN);
• Total bilirubin (TBIL) < 1.5 ULN;
• Serum creatinine (CR) <1.5 ULN or creatinine clearance (CCR) ≥50ml/min;
• Serum albumin ≥30g/L;
• International Normalized ratio (INR), prothrombin time (PT), activated partial thrombin time (APTT) ≤1.5ULN;
• Thyrotropin (TSH) ≤ULN;If abnormal, T3 and T4 levels should be investigated, and normal levels can be included.

5.cardiac color ultrasound: Left ventricular ejection fraction (LVEF) ≥50%. 6.Hypertension was well controlled. 7.Female participants of reproductive age should agree to use contraception during the study period and for 6 months after the study ends; Serum pregnancy test was negative within 7 days prior to study enrollment,and should be Non-lactation stage. Male subjects should agree to use contraception during the study period and for 6 months after the study ends.

Exclusion criteria

• 1.Combined disease or history

• .Present or present with other malignancies within 3 years.
• .Have multiple factors affecting oral medication (such as inability to swallow, chronic diarrhea, or intestinal obstruction)
• .Gastrointestinal bleeding or perforation occurred during the first 4 weeks of enrollment
• .Patients with ulcerative colitis, Crohn's disease, and active inflammatory bowel disease during the first 4 weeks of enrollment
• .Uncontrolled pleural effusion, ascites, and moderate or greater pericardial effusion
• .Unmitigated toxic reactions above grade 1 of CTC AE due to any previous treatment, excluding alopecia.
• .Received major surgical treatment or significant traumatic injury within 28 days prior to enrollment
• .Patients with hematemesis, hematochezia, or any bleeding event ≥ CTCS AE level 3 within the previous 3 months, or with any signs of bleeding or history determined by the investigator to be ineligible for enrollment
• .Arteriovenous thrombosis occurred within 6 months, such as cerebrovascular accident, pulmonary embolism, etc
• .A history of psychotropic substance abuse and inability to abstain
• .Subjects with any severe and/or uncontrolled disease, including

• Uncontrolled hypertension
• Unstable angina pectoris / ≥ grade 2 cardiogenic chest pain;Myocardial infarction occurred within 12 months before randomization;≥ grade 2 heart failure;Restrictive heart disease;≥ grade 2 atrioventricular block, arrhythmia that cannot be stably controlled with drugs.
• Active infection
• Decompensated cirrhosis, active hepatitis;
• Renal failure requires hemodialysis or peritoneal dialysis
• A history of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation

h.Diabetes with poorly controlled i.Urine routine showed urine protein ≥++, and 24h albuminuria quantitative > 1.0 g g.History of neurological or psychiatric disorders 2.Subjects who, in the investigator's judgment, have a concomitant medical condition that seriously endangers subjects' safety or interferes with the completion of the study, or are deemed unsuitable for enrollment for other reasons.