An Open, Single-center Clinical Study of Surufatinib Combined With Temozolomide and S-1 in the First-line Treatment of Advanced Neuroendocrine Tumors

Inclusion Criteria:

• Aged 18-75years (inclusive);

• Histopathologically confirmed diagnosis of advanced MGMT0/1+ (G1, G2 or G3)neuroendocrine tumor (locally advanced, unresectable or distant metastasis);

• Previously untreated with systemic therapy;

• Have at least one measurable lesion according to RECIST v1.1;

• ECOG performance status: 0-2(determined by investigator);

• Expected survival time > 3 months;

• Adequate hepatic, renal, heart, and hematologic functions;

• Urine protein < ++ . If Urine protein ≥ ++ ,the amount of urine protein in 24 hours ≤1.0g;

• Before the first dose, serum HCG examination of potential childbearing-women must benegative; Men/Women of childbearing potential must agree to use a highly effectivecontraceptive method (such as double barrier contraceptive method, condom, oral orinjectable contraceptives and intrauterine device) throughout treatment and for atleast 90 days after study completion.

Exclusion Criteria:

• Neuroendocrine cancer, adenocarcinoid, goblet cell carcinoid,

• Functional NETs which need to control symptoms by long-acting somatostatinanalogues;

• Received a major surgery which requires at least 3 weeks after recovery time, toundergo surgery on treatment of this research within 4 weeks prior to treatment;

• Have uncontrolled hypertension, defined as systolic blood pressure >140 mmHg ordiastolic blood pressure >90 mm Hg, while under anti-hypertension treatment;

• Patients with active ulcer, intestinal perforation and intestinal obstruction;

• With active bleeding or bleeding tendency;

• Severe history of cardiovascular and cerebrovascular diseases;

• Other malignancies diagnosed within the previous 5 years, except basal cellcarcinoma or cervical carcinoma in situ after radical resection.