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

NCT07018063 | Not Yet Recruiting Phase 2

• 1 other identifier: PKUPH-EOGC-001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (6)

• 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

Study Arms (1)

Neoadjuvant nab-SOX plus Sintilimab

EXPERIMENTAL

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.

Drug: nab-paclitaxel; Drug: oxaliplatin; Drug: S-1; Drug: sintilimab; Procedure: D2 Gastrectomy

Interventions

nab-paclitaxel DRUG

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.

Neoadjuvant nab-SOX plus Sintilimab

oxaliplatin DRUG

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.

Neoadjuvant nab-SOX plus Sintilimab

S-1 DRUG

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)

Neoadjuvant nab-SOX plus Sintilimab

sintilimab DRUG

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.

Neoadjuvant nab-SOX plus Sintilimab

D2 Gastrectomy PROCEDURE

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.

Neoadjuvant nab-SOX plus Sintilimab

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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;

Sponsors & Collaborators

• zhoujing: lead

Study Sites (1)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

Related Publications (12)

• Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. doi: 10.1097/01.sla.0000133083.54934.ae.

  PMID: 15273542 BACKGROUND

• Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, Bottcher K, Siewert JR, Hofler H. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003 Oct 1;98(7):1521-30. doi: 10.1002/cncr.11660.

  PMID: 14508841 BACKGROUND

• Watson S, de la Fouchardiere C, Kim S, Cohen R, Bachet JB, Tournigand C, Ferraz JM, Lefevre M, Colin D, Svrcek M, Meurisse A, Louvet C. Oxaliplatin, 5-Fluorouracil and Nab-paclitaxel as perioperative regimen in patients with resectable gastric adenocarcinoma: A GERCOR phase II study (FOXAGAST). Eur J Cancer. 2019 Jan;107:46-52. doi: 10.1016/j.ejca.2018.11.006. Epub 2018 Dec 7.

  PMID: 30529902 BACKGROUND

• Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. doi: 10.1016/S2468-1253(16)30219-9. Epub 2017 Jan 19.

  PMID: 28404157 BACKGROUND

• Zhang C, Tang R, Zhu H, Ge X, Wang Y, Wang X, Miao L. Comparison of treatment strategies and survival of early-onset gastric cancer: a population-based study. Sci Rep. 2022 Apr 15;12(1):6288. doi: 10.1038/s41598-022-10156-5.

  PMID: 35428811 BACKGROUND

• Liu L, Lin J, Zhao J, Yan P. Analysis of clinicopathologic characteristics and prognosis of gastric cancer in patients <40 years. Medicine (Baltimore). 2023 Aug 25;102(34):e34635. doi: 10.1097/MD.0000000000034635.

  PMID: 37653814 BACKGROUND

• Liu JD, Ye BT, Fu M, Zhang Q, Chen H, Sun J, Cai TY, Wang ZM, He HY, Zhao JJ, Li HJ, Wang XF, Sun YH. [Clinicopathological and molecular diagnostic features of early-onset gastric cancer: a study based on data from a single-center dedicated gastric cancer database]. Zhonghua Wei Chang Wai Ke Za Zhi. 2023 Oct 25;26(10):963-967. doi: 10.3760/cma.j.cn441530-20230603-00190. Chinese.

  PMID: 37849267 BACKGROUND

• Pocurull A, Herrera-Pariente C, Carballal S, Llach J, Sanchez A, Carot L, Botargues JM, Cuatrecasas M, Ocana T, Balaguer F, Bujanda L, Moreira L. Clinical, Molecular and Genetic Characteristics of Early Onset Gastric Cancer: Analysis of a Large Multicenter Study. Cancers (Basel). 2021 Jun 23;13(13):3132. doi: 10.3390/cancers13133132.

  PMID: 34201547 BACKGROUND

• Rompen IF, Nienhuser H, Crnovrsanin N, Musa J, Haag GM, Longerich T, Fiedler T, Muller-Stich BP, Sisic L, Billeter AT. Clinical Characteristics and Oncological Outcomes of Surgically Treated Early-Onset Gastric Adenocarcinoma - a Retrospective Cohort Study. J Cancer. 2023 May 21;14(9):1470-1478. doi: 10.7150/jca.82876. eCollection 2023.

  PMID: 37325055 BACKGROUND

• Qu X, Zhao X, Liu Y, Wang N, Zhang L, Zhu X, Dong Q, Liu J, Shi Y. The clinicopathological characteristics of early-onset gastric cancer and its evolutionary trends: a retrospective study. Am J Cancer Res. 2022 Jun 15;12(6):2757-2769. eCollection 2022.

  PMID: 35812046 BACKGROUND

• Ning FL, Zhang NN, Zhao ZM, Du WY, Zeng YJ, Abe M, Pei JP, Zhang CD. Global, Regional, and National Burdens with Temporal Trends of Early-, Intermediate-, and Later-Onset Gastric Cancer from 1990 to 2019 and Predictions up to 2035. Cancers (Basel). 2022 Nov 3;14(21):5417. doi: 10.3390/cancers14215417.

  PMID: 36358835 BACKGROUND

• Lumish MA, Walch H, Maron SB, Chatila W, Kemel Y, Maio A, Ku GY, Ilson DH, Won E, Li J, Joshi SS, Gu P, Schattner MA, Laszkowska M, Gerdes H, Jones DR, Sihag S, Coit DG, Tang LH, Strong VE, Molena D, Stadler ZK, Schultz N, Janjigian YY, Cercek A. Clinical and molecular characteristics of early-onset vs average-onset esophagogastric cancer. J Natl Cancer Inst. 2024 Feb 8;116(2):299-308. doi: 10.1093/jnci/djad186.

  PMID: 37699004 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Stomach Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Oxaliplatin; S 1 (combination); sintilimab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• JING ZHOU, M.D.

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

XUESONG ZHAO, M.D.

CONTACT

86+01088326600; xuesongzhao@bjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Medical Oncologist, Department of Gastrointestinal Surgery, Peking University People's Hospital

Model Details: All enrolled participants will receive the investigational treatment. No control group is included.

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: June 12, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): June 1, 2030
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD will be available beginning 6 months after publication and ending 5 years after publication.
• Access Criteria: Researchers requesting data sharing should send their research proposals to xuesongzhao@bjmu.edu.cn. Access to the data will require consultation with the principal investigator and the signing of a data use agreement.

Locations

CN (1)