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

Phase 2Not Yet RecruitingNCT07658872

Sichuan University120 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

Gastric Adenocarcinoma Esophagogastric Junction Adenocarcinoma

Interventions

fruquintinib + sintilimab + SOXDRUG

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.

Sinitilimab+SOXDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Perioperative

Secondary Outcomes

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;

Time frame: 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)

Time frame: 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;

Time frame: Perioperative

R0 resection

R0 resection defined as microscopically margin-negative resection

Time frame: Perioperative

overall survival (OS)

OS defined as the time from randomization to death from any cause;

Time frame: 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.

Time frame: 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)

Time frame: 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

Time frame: 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).

Time frame: Through study completion, an average of 2 years

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts