Perioperative Fruquintinib Combined With Sintilimab and SOX for Locally Advanced Gastric or GEJ Adenocarcinoma

Perioperative Fruquintinib Combined With Sintilimab and SOX Versus Sintilimab and SOX for Resectable Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma：A Multicenter,Open-label, Randomized Controlled Phase II Clinical Study

The purpose of this clinical trial is to evaluate whether perioperative fruquintinib combined with sintilimab and SOX is effective in treating locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. The study will also assess the safety profile of this treatment regimen.

Primary Objective:

To determine whether perioperative fruquintinib combined with sintilimab and SOX improves the pathological complete response (pCR) rate compared with sintilimab plus SOX in patients with locally advanced gastric or GEJ adenocarcinoma.

Study Design:

Participants will be randomly assigned to receive either fruquintinib combined with sintilimab and SOX or sintilimab plus SOX to evaluate the potential added benefit of fruquintinib in this setting.

Participation Details:

Participants will receive the assigned treatment (fruquintinib combined with sintilimab and SOX or sintilimab plus SOX) every 21 days for approximately 3 months.

They will visit the clinic once every 3 weeks for evaluations, laboratory tests, and monitoring.

Participants will be asked to keep a daily diary to record any symptoms or side effects experienced during the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma; Esophagogastric Junction Adenocarcinoma
• Intervention / Treatment: Drug: fruquintinib + sintilimab + SOX; Drug: Sinitilimab+SOX

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongfeng Gou, PhD; Phone Number: +86-18980602292; Email: gouhongfeng1977@wchscu.cn
• Study Contact Backup: Name: Wen Nie, Ph.D; Phone Number: +86-02885423297; Email: wennie1228@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-75 years.
2. Histologically confirmed gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
4. Clinically staged as T3-4a N0-3M0 by computed tomography (CT) or magnetic resonance imaging (MRI).
5. Considered eligible for curative resection.
6. No prior antitumor therapy for the current disease.
7. Adequate organ function, including hepatic, renal, and bone marrow function, as per prespecified laboratory criteria.
8. Expected survival of ≥6 months.

Exclusion Criteria:

1. Known mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumor.
2. Uncontrolled hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥ 90 mmHg despite optimized antihypertensive therapy, or hypertension complicated by acute events (e.g., hypertensive crisis, hypertensive encephalopathy) that cannot be stably controlled.
3. Tumor lesions with a bleeding tendency, including but not limited to: active ulcerative tumor lesions, hematemesis within 2 months prior to informed consent, high risk of major gastrointestinal bleeding as determined by the investigator.
4. History of thromboembolic or arterial/venous vascular events within 6 months prior to enrollment, such as cerebrovascular events (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism.
5. Gastrointestinal perforation or gastrointestinal obstruction within 6 months prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fruquintinib + Sintilimab + SOX	Drug: fruquintinib + sintilimab + SOX; Fruquintinib, 4mg po d1-14 q3w, four 3-week cycles were administered; S-1 (administered orally twice daily on days 1-14 of each 21-day cycle, with the daily dose determined by body surface area: <1.25 m², 80 mg/day; ≥1.25 to <1.5 m², 100 mg/day; ≥1.5 m², 120 mg/day), four 3-week cycles were administered. Oxaliplatin (130 mg/m², administered intravenously on day 1), four 3-week cycles were administered.
Active Comparator: Sintilimab + SOX	Drug: Sinitilimab+SOX; S-1 (administered orally twice daily on days 1-14 of each 21-day cycle, with the daily dose determined by body surface area: <1.25 m², 80 mg/day; ≥1.25 to <1.5 m², 100 mg/day; ≥1.5 m², 120 mg/day), four 3-week cycles were administered. Oxaliplatin (130 mg/m², administered intravenously on day 1), four 3-week cycles were administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total pathological complete response (pCR)	Total pathological complete response (pCR; ypT0) assessed by investigators, defined as the complete absence of tumor cells in the primary tumor on pathological examination.	Perioperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	Event-free survival (EFS), defined as the time from randomization to the first occurrence of relapse, metastasis, or death from any cause;	Through study completion, an average of 2 years
TRAEs	Treatment-related adverse events (TRAEs) with potential immunologic etiology were categorized and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0)	Through study completion,an average of 2 years
major pathologic response（MPR)	major pathologic response（MPR) defined as ≤10% residual viable tumor cells in the resected primary tumor specimen after neoadjuvant therapy;	Perioperative
R0 resection	R0 resection defined as microscopically margin-negative resection	Perioperative
overall survival (OS)	OS defined as the time from randomization to death from any cause;	Through study completion,an average of 2 years
Expression of Predictive Biomarkers Associated With Treatment Response	Predictive biomarkers including PD-L1 expression, Epstein-Barr virus status, tumor mutational burden, and immune-related biomarkers will be analyzed for association with pathological and radiographic treatment response.	Baseline through study completion, an average of 2 years
Change in Quality of Life Assessed by EORTC QLQ-C30	Quality of life was assessed using the EORTC QLQ-C30 questionnaires, administered at three time points: within one week before initiation of neoadjuvant therapy, within one week before the fourth neoadjuvant therapy cycle, and at 30 days postoperatively (±3 days)	Through study completion, an average of 2 years
disease-free survival (DFS)	DFS defined as the time from the post-surgery baseline scan to the first occurrence of relapse, metastasis, or death from any cause	From date of post-surgery until the date of first occurrence of relapse, metastasis, or date of death from any cause, whichever came first, assessed up to 100 months
Change in Quality of Life Assessed by EORTC QLQ-STO22	Quality of life was assessed using the EORTC QLQ-STO22 questionnaires, administered at three time points: within one week before initiation of neoadjuvant therapy, within one week before the fourth neoadjuvant therapy cycle, and at 30 days postoperatively (±3 days).	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Sichuan University
• Investigators: Principal Investigator: Hongfeng Gou, Ph.D, Gastric Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu 610041, Sichuan, China.

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): May 19, 2027
• Study Completion (Estimated): April 6, 2028

Study Registration Dates

• First Submitted: May 31, 2026
• First Submitted That Met QC Criteria: June 15, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Gastric Cancer; neoadjuvant treatment; Fruquintinib
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; sintilimab; HMPL-013
• Other Study ID Numbers: HUAXI-GC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data (IPD) may not be shared due to privacy and confidentiality concerns, legal or ethical restrictions, limitations in data sharing agreements or consent, intellectual property rights, commercial interests, or because of technical and resource constraints related to data anonymization and sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No