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

Study Overview
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Brief Summary
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This is a prospective, open, single-center study evaluating the efficacy and safety of surufatinib Combined With Temozolomide and S-1 as the first-line treatment of advanced neuroendocrine tumors

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

Conditions
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Neuroendocrine Tumors

Intervention / Treatment
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* Drug: Surufatinib Combined With Temozolomide and S-1


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Surufatinib Combined With Temozolomide and S-1
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surufatinib Combined With Temozolomide and S-1<br>Patients will receive surufatinib combined with temozolomide and S-1 once every three weeks as the second-line treatment until disease progression or intolerable toxicity or patients withdrawal of consent. Phase I: DLTs of surufatinib combined with temozolomide and S-1 will be evaluated based on NCI CTCAE v 5.0 in the first cycle. | Drug: Surufatinib Combined With Temozolomide and S-1<br>* Phase I: Surufatinib: 250mg, QD, PO, Q3W; Temozolomide: 200-300mg, d10-d14, QD, PO, Q3W; S-1: 40-60mg, d1-d14, BID, PO, Q3W. Phase II: Surufatinib, Temozolomide and S-1：RP2D<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | the proportion of patients with complete response or partial response, using RESIST v1.1 | approximately 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | time from first-dose to the first documented disease progression or death | approximately 1 years | 
| Disease Control Rate (DCR) | the proportion of patients with complete response, partial response or stable disease, using RESIST v1.1 | approximately 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surufatinib, Temozolomide and S-1, First-line treatment