Neoadjuvant Nab-Paclitaxel Plus Oxaliplatin, S-1, and Sintilimab in Early-Onset Resectable Gastric Cancer

Phase 2

Not yet recruiting

• Conditions: Gastric (Cardia, Body) Cancer; Stomach Adenocarcinoma; Locally Advanced
• Interventions: Drug: nab-paclitaxel; Drug: oxaliplatin; Drug: S-1; Drug: sintilimab; Procedure: D2 Gastrectomy

• Registration Number: NCT07018063
• Lead Sponsor: zhoujing

Brief Summary

This study aims to evaluate the effectiveness and safety of a preoperative treatment (called neoadjuvant therapy) combining four drugs-nab-paclitaxel, oxaliplatin, S-1, and sintilimab-for patients with locally advanced, resectable early-onset gastric cancer (diagnosed at age 45 or younger).

All participants will receive this drug combination before undergoing surgery to remove the tumor. The goal is to shrink the tumor, increase the chance of complete surgical removal, and improve long-term outcomes.

This is a single-arm, open-label, phase II clinical trial, meaning all participants will receive the same treatment, and both doctors and patients will know what drugs are being used. The study is being conducted at Peking University People's Hospital.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-04
• Study First Submitted QC: 2025-06-04
• Last Update Submitted: 2025-06-04
• Study First Posted: 2025-06-12
• Last Update Posted: 2025-06-12
• Study Start: 2025-10-01
• Primary Completion: 2027-12-30
• Study Completion: 2030-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• Participants must meet all of the following inclusion criteria:
• Male or female, aged ≥16 and ≤45 years;
• Karnofsky performance score ≥70% or ECOG performance status 0-1;
• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (GEJ).
• For gastric body cancer: clinical stage cT3-T4a N+ M0;
• For GEJ cancer: clinical stage cT2-T4a N+ M0;
• For cT4b Nany M0 cases: location may be gastric body or GEJ.
• Staging is based on contrast-enhanced CT, MRI (if needed), and endoscopic ultrasonography (EUS) (if needed);
• Assessed as resectable after multidisciplinary team (MDT) discussion;
• Surgical evaluation confirms that D2 radical gastrectomy is feasible;
• Sufficient physical condition and organ function to tolerate major abdominal surgery;
• Baseline laboratory tests meet the following criteria:
• Hemoglobin ≥90 g/L
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L
• Platelets ≥100×10⁹/L
• ALT and AST ≤2.5× upper limit of normal (ULN)
• Alkaline phosphatase (ALP) ≤2.5× ULN
• Total bilirubin <1.5× ULN
• Serum creatinine <1× ULN
• Serum albumin ≥30 g/L
• No severe comorbidities that may limit life expectancy to <3 years;
• Participant is willing and able to comply with the study protocol during the study period;
• Written informed consent must be signed before screening. Participants must understand their right to withdraw at any time without any loss of benefits;
• Willing to provide blood and tissue samples.

Exclusion Criteria

• Participants meeting any of the following criteria will be excluded:
• Patients with HER-2 positive gastric cancer, as determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH);
• Patients with dMMR (deficient mismatch repair) or MSI-H (microsatellite instability-high) tumors, as determined by IHC;
• Pregnant or breastfeeding women;
• Prior treatment for gastric cancer with cytotoxic chemotherapy, radiotherapy, or immunotherapy;
• History of other malignancies within the past 5 years;
• Active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis;
• Active inflammatory bowel diseases, such as Crohn's disease or ulcerative colitis;
• Currently receiving systemic corticosteroids or other immunosuppressive therapy;
• Prior organ transplantation or use of anti-rejection medications;
• Active tuberculosis, HIV infection, or severe active hepatitis B or C;
• History of uncontrolled epilepsy, central nervous system disorders, or psychiatric illnesses that, in the investigator's judgment, may interfere with informed consent or compliance with oral medication;
• Clinically significant (active) cardiac diseases, including symptomatic coronary artery disease, NYHA class II or above congestive heart failure , severe arrhythmias requiring medical intervention, or myocardial infarction within the past 12 months;
• Presence of upper gastrointestinal obstruction that may impair the oral intake or absorption of S-1;
• Severe uncontrolled recurrent infections or other uncontrolled serious comorbidities;
• Use of any investigational drugs within 4 weeks prior to study enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant nab-SOX plus Sintilimab	nab-paclitaxel	Patients will receive three 3-week cycles of neoadjuvant chemotherapy consisting of nab-paclitaxel 125 mg/m² IV on day 1, oxaliplatin 85 mg/m² IV on day 1, and S-1 80-120 mg/day orally on days 2-15, plus sintilimab 200 mg IV on day 1. D2 gastrectomy will be performed 3-6 weeks after neoadjuvant therapy.
Neoadjuvant nab-SOX plus Sintilimab	oxaliplatin	Patients will receive three 3-week cycles of neoadjuvant chemotherapy consisting of nab-paclitaxel 125 mg/m² IV on day 1, oxaliplatin 85 mg/m² IV on day 1, and S-1 80-120 mg/day orally on days 2-15, plus sintilimab 200 mg IV on day 1. D2 gastrectomy will be performed 3-6 weeks after neoadjuvant therapy.
Neoadjuvant nab-SOX plus Sintilimab	S-1	Patients will receive three 3-week cycles of neoadjuvant chemotherapy consisting of nab-paclitaxel 125 mg/m² IV on day 1, oxaliplatin 85 mg/m² IV on day 1, and S-1 80-120 mg/day orally on days 2-15, plus sintilimab 200 mg IV on day 1. D2 gastrectomy will be performed 3-6 weeks after neoadjuvant therapy.
Neoadjuvant nab-SOX plus Sintilimab	sintilimab	Patients will receive three 3-week cycles of neoadjuvant chemotherapy consisting of nab-paclitaxel 125 mg/m² IV on day 1, oxaliplatin 85 mg/m² IV on day 1, and S-1 80-120 mg/day orally on days 2-15, plus sintilimab 200 mg IV on day 1. D2 gastrectomy will be performed 3-6 weeks after neoadjuvant therapy.
Neoadjuvant nab-SOX plus Sintilimab	D2 Gastrectomy	Patients will receive three 3-week cycles of neoadjuvant chemotherapy consisting of nab-paclitaxel 125 mg/m² IV on day 1, oxaliplatin 85 mg/m² IV on day 1, and S-1 80-120 mg/day orally on days 2-15, plus sintilimab 200 mg IV on day 1. D2 gastrectomy will be performed 3-6 weeks after neoadjuvant therapy.

Primary Outcome Measures

Name	Time	Method
Pathological complete response (pCR) rate after neoadjuvant therapy	At the time of surgery, approximately 13-16 weeks from the start of neoadjuvant therapy	Pathological complete response (pCR) is defined as the absence of residual invasive tumor cells in the resected stomach and lymph nodes (ypT0N0), as assessed by centralized pathological review following D2 radical gastrectomy.

Secondary Outcome Measures

Name	Time	Method
R0 resection rate after neoadjuvant therapy and surgery	At the time of surgery, approximately 13-16 weeks from the start of treatment	The proportion of patients achieving R0 resection, defined as complete macroscopic and microscopic tumor removal with negative margins.
Major pathological response (MPR) rate based on Becker tumor regression grade	At the time of surgery, approximately 13-16 weeks from the start of treatment	The proportion of patients with residual tumor cells ≤10% in the primary tumor bed, corresponding to Becker TRG 1a and 1b categories, assessed by pathological review.
3-year disease-free survival (DFS)	Up to 36 months after surgery	DFS is defined as the time from informed consent to the first occurrence of tumor recurrence, metastasis, or death from any cause.
3-year overall survival (OS)	Up to 36 months after surgery	OS is defined as the time from informed consent to death from any cause. Censoring will occur at the last follow-up for event-free patients.
Incidence of treatment-related grade 3 or higher adverse events	From initiation of treatment to surgery, approximately 12-15 weeks	Frequency and types of grade 3 or higher adverse events as defined by NCI CTCAE v5.0, recorded during neoadjuvant therapy to evaluate treatment safety.
Incidence of major postoperative complications	From surgery until hospital discharge or 30 days postoperatively, whichever is longer	Postoperative complications will be recorded and classified using the Clavien-Dindo classification system, including but not limited to anastomotic leakage, surgical site infection, and postoperative bleeding.

Trial Locations

Locations (1)

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China