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

Recruiting

• Conditions: Gastric Neuroendocrine Carcinoma
• Interventions: Drug: Sintilimab，Surufatinib

• Registration Number: NCT06102746
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2023-04-10
• Status Verified: 2023-10
• Study First Submitted: 2023-10-18
• Study First Submitted QC: 2023-10-22
• Last Update Submitted: 2023-10-22
• Study First Posted: 2023-10-26
• Last Update Posted: 2023-10-26
• Primary Completion: 2026-04-10
• Study Completion: 2026-04-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Sintilimab + Surufatinib + EP	Sintilimab，Surufatinib	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;

Primary Outcome Measures

Name	Time	Method
ORR	3 years	It refers to the proportion of patients whose tumors have shrunk to a certain amount and maintained for a certain period of time, including CR and PR cases. Solid tumor response assessment criteria (RECIST 1.1 criteria) were used to evaluate objective tumor response. Participants had to have a measurable tumor lesion at baseline, and response criteria were classified as complete response (CR), partial response (PR), stable disease (SD), and disease progression (PD) according to RECIST 1.1 criteria.

Secondary Outcome Measures

Name	Time	Method
PFS	3 years	From the date of enrollment to the date of the first onset of disease progression or death from any cause, whichever comes first. If the subject does not develop disease progression during the trial period, PFS is defined as the last date until the subject's last confirmed progression-free survival. Participants who discontinue the trial for reasons other than disease progression (no follow-up imaging) and those who receive post-trial treatment will be subject to data deletion based on the time of discontinuation or the time of initiation of post-trial treatment. When subjects do not use the time of discontinuation of the trial or the time of initiation of post-trial treatment as data deletion, pre-planned sensitivity statistical analyses will further confirm PFS based only on the time of the event at which image-confirmed progression occurs. New occurrence of other tumors is not considered a disease progression event and is not considered for data deletion. If the imaging examination

Trial Locations

Locations (1)

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin, China