Clinical Study of Surufatinib Plus Sintilimab Combined With Chemotherapy in the Treatment of Advanced Gastric Neuroendocrine Carcinoma

A Single-center, Open Phase II Clinical Study of Surufatinib Plus Sintilimab Combined With Chemotherapy in the Treatment of Advanced Gastric Neuroendocrine Carcinoma

This study aims to explore whether the combination of surufatinib (anti-angiogenic therapy) and sintilimab (PD-1 inhibitor) on the basis of EP regimen can further improve the effective rate and survival time of first-line treatment for patients with advanced gastric neuroendocrine carcinoma, and explore the safety and tolerability of this regimen.

In this study, patients with advanced gastric neuroendocrine carcinoma were selected as the research object. Based on the standard EP regimen, the combination of surufatinib (anti-angiogenic therapy) and sintilimab (PD-1 inhibitor) could further improve the effective rate and survival time of patients, and explore the safety and tolerability of this treatment regimen.

Patients with advanced gastric neuroendocrine carcinoma who have not received systematic treatment will be treated with the following protocols:

Sintilimab: 200mg intravenously administered on day 1; Surufatinib: 200mg/ day orally, taken continuously; Etoposide: 1, 2, 3 days of continuous administration, 100mg/m2, intravenous infusion; Cisplatin: 75mg/m2 on day 1, or 25mg/m2 on day 1, 2, and 3, intravenous infusion; One treatment cycle every 21 days; Etoposide and cisplatin were used for a maximum of 4 cycles, after which maintenance therapy of solantinib and sindellizumab was administered, and the longest treatment cycle was 13 cycles (a total of 1 year). Patients received regular and periodic reviews, and imaging assessments were performed every 6 weeks after enrollment in the study. Safety will be evaluated by AE and laboratory tests. After disease progression, all patients were followed up with their secondary survival status every 3 months until death.

Inclusion Criteria:

To be enrolled in this trial, patients must meet all of the following inclusion criteria:

1. Locally advanced or metastatic gastric neuroendocrine carcinoma (NEC), hyperproliferative neuroendocrine tumor (NET G3) or mixed neuroendocrino-non-neuroendocrine tumor (MiNEN), as demonstrated by pathology (WHO classification criteria 2019), may also be included;

2. Have not received systematic anti-tumor therapy before;

3. Have received radical treatment in the past and have no treatment interval from the end of chemotherapy, radiotherapy, or chemoradiotherapy to relapse for at least 6 months (the end time of the last chemotherapy cycle/the end time of the last radiotherapy);

4. There are measurable lesions defined by the RECIST 1.1 standard;

5. At least 18 years old;

6. ECOG physical condition: 0-1 score;

7. Expected survival of more than 3 months;

8. If the major organs function normally, the following criteria are met:

   1. Blood routine examination: hemoglobin (Hb) ≥90g/L; Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelet (PLT) ≥100×10^9/L; White blood cell count (WBC) ≥3.0×10^9/L;
   2. Biochemical examination: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (tumor liver metastasis, ≤5×ULN); Serum total bilirubin (TBIL) ≤1.5×ULN (Gilbert syndrome subjects, ≤3×ULN); Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥50ml/min;
   3. Coagulation function: activated partial thromboplastin time (APTT), International Standardized ratio (INR), prothrombin time (PT) ≤1.5×ULN;

9. The subjects voluntarily joined the study, signed the informed consent, and the compliance was good.

Exclusion Criteria:

Patients with any of the following conditions were excluded from the study:

1. The presence of a serious illness or medical condition, including but not limited to the following:

   1. Known recurrence in situ or metastasis at any other site;
   2. systemic active infection (i.e. infection resulting in body temperature ≥38 ° C);
   3. Clinically significant intestinal obstruction, pulmonary fibrosis, renal failure, liver failure, or symptomatic cerebrovascular disease;
   4. Severe/unstable angina, New York Heart Association (NYHA) Class III or IV symptomatic congestive heart failure;
   5. Clinically significant gastrointestinal bleeding;
   6. Known presence of human immunodeficiency virus (HIV) or acquired conventional immunodeficiency syndrome (AIDS) - associated disease, or active hepatitis B or C;

2. Pregnant or lactating women;

3. The researcher considers it inappropriate to enter this study.