Clinical trial NCT07018063: Neoadjuvant Nab-Paclitaxel Plus Oxaliplatin, S-1, and Sintilimab in Early-Onset Resectable Gastric Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Gastric (Cardia, Body) Cancer
Stomach Adenocarcinoma
Locally Advanced
Keywords: gastric cancer
Neoadjuvant therapy
Early-onset gastric cancer
Immunotherapy
Chemotherapy
Single-arm trial
Phase II trial
Perioperative treatment
China
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2025-06-12
Enrollment: 35
Sex: ALL
Minimum age (years): 16
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All enrolled participants will receive the investigational treatment. No control group is included.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pathological complete response (pCR) rate after neoadjuvant therapy
timeFrame: At the time of surgery, approximately 13-16 weeks from the start of neoadjuvant therapy
Secondary outcomes:
measure: R0 resection rate after neoadjuvant therapy and surgery
timeFrame: At the time of surgery, approximately 13-16 weeks from the start of treatment
measure: Major pathological response (MPR) rate based on Becker tumor regression grade
timeFrame: At the time of surgery, approximately 13-16 weeks from the start of treatment
measure: 3-year disease-free survival (DFS)
timeFrame: Up to 36 months after surgery
measure: 3-year overall survival (OS)
timeFrame: Up to 36 months after surgery
measure: Incidence of treatment-related grade 3 or higher adverse events
timeFrame: From initiation of treatment to surgery, approximately 12-15 weeks
measure: Incidence of major postoperative complications
timeFrame: From surgery until hospital discharge or 30 days postoperatively, whichever is longer
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: JING ZHOU, M.D.
role: PRINCIPAL_INVESTIGATOR
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