Efficacy and Safety of Neoadjuvant Nab-Paclitaxel Combined With Oxaliplatin, S-1, and Sintilimab in Patients With Locally Advanced Resectable Early-onset Gastric Cancer: A Phase II, Single-Arm, Open-Label Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Pathological complete response (pCR) rate after neoadjuvant therapy
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Neoadjuvant nab-SOX plus 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.
干预措施: nab-paclitaxel (Drug)
Neoadjuvant nab-SOX plus 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.
干预措施: oxaliplatin (Drug)
Neoadjuvant nab-SOX plus 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.
干预措施: S-1 (Drug)
Neoadjuvant nab-SOX plus 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.
干预措施: sintilimab (Drug)
Neoadjuvant nab-SOX plus 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.
干预措施: D2 Gastrectomy (Procedure)
结局指标
主要结局
Pathological complete response (pCR) rate after neoadjuvant therapy
时间窗: 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.
次要结局
- R0 resection rate after neoadjuvant therapy and surgery(At the time of surgery, approximately 13-16 weeks from the start of treatment)
- 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)
- 3-year disease-free survival (DFS)(Up to 36 months after surgery)
- 3-year overall survival (OS)(Up to 36 months after surgery)
- Incidence of treatment-related grade 3 or higher adverse events(From initiation of treatment to surgery, approximately 12-15 weeks)
- Incidence of major postoperative complications(From surgery until hospital discharge or 30 days postoperatively, whichever is longer)
研究者
zhoujing
Chief Medical Oncologist, Department of Gastrointestinal Surgery, Peking University People's Hospital
Peking University People's Hospital