A Phase II Clinical Study of Fruquintinib Combined With S-1 for Advanced Esophageal Squamous Cell Carcinoma

Investigators conduct the clinical trial to further explore the efficacy and safety of Fruquintinib combined with S-1 in treating recurrent or metastatic esophageal squamous cell carcinoma after the failure of conventional treatments.

Inclusion Criteria:Male or female patients, age:≥18 years oldImageology diagnosed with refractory or metastatic esophageal squamous cell carcinomaDisease progression after the last dose of the first-line therapy (with immunotherapy, without fluoropyrimidine)At least one measurable lesion (RECIST1.1)Good performance status Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 2Life expectancy of more than 12 weeksThe test value for bone marrow, liver and renal function evaluation within 7 days prior to first dosing should meet requirementsNegative of blood pregnancy test within 7 days prior to first dosing for fertile female patients. Fertile female and male patients agree to use effective contraceptive methods during the study and within 6 months post to the last dose, such as double barrier contraception, condoms, oral or injection contraceptives, intrauterine devices, abstinence, etc. All female patients will be considered fertile unless the female patient has natural menopause or has undergone artificial menopause or sterilization (hysterectomy, bilateral appendage resection);Signed informed consentExclusion Criteria:Absolute neutrophil count (ANC) <1.5×109/L, platelet count <75×109/L, and hemoglobin <9g/dLSerum total bilirubin >1.5× the upper limit of normal (ULN)Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >2.5×ULNCreatinine > 1.5 × ULN or creatinine clearance <50 mL/minActivated partial thromboplastin time (APTT)> 1.5 × ULNThe investigators determined clinically significant severe electrolyte abnormalities.Proteinuria ≥ 2+ (1.0g/24hr)Drug uncontrollable hypertension, defined as systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHgThe patients have active ulcer of stomach and duodenum, ulcerative colitis and other digestive tract diseases or unresectable tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding and perforation, as judged by investigators; or the existence of gastrointestinal perforation or gastrointestinal fistula uncured post to previous surgical treatmentPatients with evidence or history of propensity to hemorrhage within 2 months prior to first dosing, regardless of severity(such as melena, hematemesis, hemoptysis, bloody stools）Arterial thrombosis or deep venous thrombosis within 6 months prior to first dosing, or thromboembolic eventsCardiovascular diseases of significant clinical significance, including, but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting within 6 months prior to first dosing, congestive heart failure with New York Heart Association (NYHA) grade ≥ 2; Left ventricular ejection fraction (LVEF) < 50%Uncontrolled malignant pleural effusion, ascites or pericardial effusionPrevious treatment with anti-vascular endothelial growth factor receptor (VEGFR) inhibitorsA history of other malignancies within 5 years prior to inclusion, except for cervical carcinoma in situ, basal or squamous cell skin cancerDistal metastasis to brainHistory of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive (copies ≥1×104/ml); known hepatitis C virus infection with HCV RNA positiveWomen who are pregnant or lactatingPatients considered unsuitable for inclusion in this study by the investigatorPatients considered a serious mental or mental abnormality