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 be negative; Men/Women of childbearing potential must agree to use a highly effective contraceptive method (such as double barrier contraceptive method, condom, oral or injectable contraceptives and intrauterine device) throughout treatment and for at least 90 days after study completion.

Exclusion Criteria:

* Neuroendocrine cancer, adenocarcinoid, goblet cell carcinoid,
* Functional NETs which need to control symptoms by long-acting somatostatin analogues;
* Received a major surgery which requires at least 3 weeks after recovery time, to undergo surgery on treatment of this research within 4 weeks prior to treatment;
* Have uncontrolled hypertension, defined as systolic blood pressure \>140 mmHg or diastolic 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 cell carcinoma or cervical carcinoma in situ after radical resection.