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

Phase 2Not Yet RecruitingNCT07018063

zhoujing35 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastric (Cardia, Body) Cancer Stomach Adenocarcinoma Locally Advanced

nab-paclitaxelDRUG

Nab-paclitaxel is administered as an intravenous (IV) infusion at a dose of 125 mg/m² on day 1 of each 3-week cycle, for a total of 3 cycles in the neoadjuvant (preoperative) setting.

oxaliplatinDRUG

Oxaliplatin is administered as an intravenous (IV) infusion at a dose of 85 mg/m² on day 1 of each 3-week cycle, for a total of 3 cycles in the neoadjuvant (preoperative) setting.

S-1DRUG

S-1 is administered orally twice daily (BID) on days 2 to 15 of each 3-week cycle, for a total of 3 cycles. The dose is based on body surface area (BSA) as follows: BSA \< 1.25 m²: 40 mg BID (total 80 mg/day); BSA 1.25-1.5 m²: 50 mg BID (total 100 mg/day); BSA \> 1.5 m²: 60 mg BID (total 120 mg/day)

sintilimabDRUG

Sintilimab is administered as an intravenous (IV) infusion at a fixed dose of 200 mg on day 1 of each 3-week cycle, for a total of 3 cycles in the neoadjuvant (preoperative) setting.

D2 GastrectomyPROCEDURE

Curative-intent D2 radical gastrectomy is performed 3 to 6 weeks after completion of neoadjuvant therapy. The procedure includes either proximal, distal or total gastrectomy depending on tumor location, with en bloc resection of the stomach and systematic D2 lymphadenectomy according to Japanese Gastric Cancer Association (JGCA) guidelines. D2 lymph node dissection involves removal of both perigastric (N1) and second-tier (N2) lymph nodes.

Eligibility

Sex: ALLMin age: 16 YearsMax age: 45 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Pathological complete response (pCR) rate after 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.

Time frame: At the time of surgery, approximately 13-16 weeks from the start of neoadjuvant therapy

Secondary Outcomes

R0 resection rate after neoadjuvant therapy and surgery

The proportion of patients achieving R0 resection, defined as complete macroscopic and microscopic tumor removal with negative margins.

Time frame: 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

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.

Time frame: At the time of surgery, approximately 13-16 weeks from the start of treatment

3-year disease-free survival (DFS)

DFS is defined as the time from informed consent to the first occurrence of tumor recurrence, metastasis, or death from any cause.

Time frame: Up to 36 months after surgery

3-year overall survival (OS)

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.

Time frame: Up to 36 months after surgery

Incidence of treatment-related grade 3 or higher adverse events

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.

Time frame: From initiation of treatment to surgery, approximately 12-15 weeks

Incidence of major postoperative complications

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.

Time frame: From surgery until hospital discharge or 30 days postoperatively, whichever is longer