Proximal Gastrectomy vs Total Gastrectomy in Locally Advanced Upper Gastric Cancer After Neoadjuvant Therapy (TJHGC01)

Comparison of Clinical Efficacy of Proximal Gastrectomy vs Total Gastrectomy in Locally Advanced Upper Gastric Cancer After SOX Combined With Anti-PD-1 Neoadjuvant Therapy：a Prospective, Multi-center, Randomised，Controlled Trial

We plan to evaluate the efficacy and safety of proximal gastric vs. total gastric radical resection after SOX combined with anti-PD-1 neoadjuvant therapy in locally advanced upper gastric cancer

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Gastric Cancer
• Intervention / Treatment: Procedure: Proximal radical gastrectomy; Procedure: Total radical gastrectomy

Detailed Description

Gastric cancer is one of the most common malignant tumors in China, and its morbidity and mortality rank among the top three for a long time.How to improve the survival rate of patients with advanced gastric cancer is the key to improve the prognosis.At present, neoadjuvant chemotherapy combined with immunosuppressants has a higher pathologic complete response (pCR) rate, reduce the clinical stage of tumors and improve the resection rate of radical surgery.Some studies have suggested that preserving partial gastric lymph nodes may enhance immunotherapy efficacy.Proximal radical gastrectomy versus total radical gastrectomy can reduce the scope of surgical resection and preserve some lymph nodes, which may contribute to long-term survival and improve postoperative quality of life of patients. It is expected to translate the short-term benefit of neoadjuvant immunotherapy into the benefit of patient overall survival (OS) rate.At the same time, our previous studies have shown that the methylation level of PD-L1 K162 can be used as a new indicator to predict the sensitivity of anti-PD -(L)1 immunotherapy, which is expected to be further confirmed in this clinical trial.Therefore, we plan to conduct a comparative study on the effectiveness and safety of proximal gastric vs. total gastric radical resection after SOX combined with anti-PD-1 neoadjuvant therapy for locally advanced upper gastric cancer, which is expected to propose new changes in surgical methods for gastric cancer and a new indicator for screening the advantages of gastric cancer immunotherapy in the era of immunotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 404
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guihua Wang; Phone Number: +86-027-83665215; Email: ghwang@tjh.tjmu.edu.cn
• Study Contact Backup: Name: lisheng chen; Phone Number: +86-13797056427; Email: clsmail1990@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital, Huazhong University of Science and Technology
      • Contact: Tongji Hospital, Huazhong University of Science and Technology; Phone Number: +86-027-83662640; Email: ims@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• To be eligible to participate in this study, all patients must meet all the following criteria:

  1. The subjects voluntarily joined the study and were able to sign the informed consent with good compliance;
  2. Age 18-75 years old (at the time of signing the informed consent), both male and female;
  3. Histologically and/or cytologically confirmed upper gastric carcinoma (adenocarcinoma), locally advanced according to AJCC Edition 8 criteria, cT3-4 or N+M0 according to endoscopic ultrasound or enhanced CT/MRI scanning (combined with diagnostic laparoscopic exploration if necessary) , and consent to neoadjuvant therapy. Investigators assessed the lesion as resectable or potentially resectable;
  4. Have not received systematic treatment for the current disease, including anti-tumor chemoradiotherapy/immunotherapy;
  5. ECOG score 0-1;
  6. Expected survival ≥6 months;
  7. Preoperative chest, abdominal, pelvic CT or PET-CT to exclude distant metastasis;
  8. The major organs function well and meet the following criteria:
  1. Blood routine examination (no blood transfusion within 14 days, no hematopoietic stimulating drugs to correct the state) : hemoglobin (Hb) ≥90g/L; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet (PLT) ≥80×109/L;
  2. Biochemical examination: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; Serum total bilirubin (TBIL) ≤1.5×ULN; Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥60mL/min;
  3. Coagulation function: activated partial thromboplastin time (APTT), International standardized ratio (INR), prothrombin time (PT) ≤1.5×ULN;
  4. Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥50%;
  5. Assessed with adequate organ function by doctors. 9. Fertile subjects must use appropriate methods of contraception during the study period and within 120 days after the end of the study, have a negative serological pregnancy test within 7 days prior to study enrollment, and must be non-lactating subjects.

Exclusion Criteria:

• To be eligible to participate in this study, all patients must meet all the following criteria:

  1. The subjects voluntarily joined the study and were able to sign the informed consent with good compliance;
  2. Age 18-75 years old (at the time of signing the informed consent), both male and female;
  3. Histologically and/or cytologically confirmed upper gastric carcinoma (adenocarcinoma), locally advanced according to AJCC Edition 8 criteria, cT3-4 or N+M0 according to endoscopic ultrasound or enhanced CT/MRI scanning (combined with diagnostic laparoscopic exploration if necessary) , and consent to neoadjuvant therapy. Investigators assessed the lesion as resectable or potentially resectable;
  4. Have not received systematic treatment for the current disease, including anti-tumor chemoradiotherapy/immunotherapy;
  5. ECOG score 0-1;
  6. Expected survival ≥6 months;
  7. Preoperative chest, abdominal, pelvic CT or PET-CT to exclude distant metastasis;
  8. The major organs function well and meet the following criteria:
  1. Blood routine examination (no blood transfusion within 14 days, no hematopoietic stimulating drugs to correct the state) : hemoglobin (Hb) ≥90g/L; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet (PLT) ≥80×109/L;
  2. Biochemical examination: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; Serum total bilirubin (TBIL) ≤1.5×ULN; Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥60mL/min;
  3. Coagulation function: activated partial thromboplastin time (APTT), International standardized ratio (INR), prothrombin time (PT) ≤1.5×ULN;
  4. Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥50%;
  5. Assessed with adequate organ function by doctors. 9. Fertile subjects must use appropriate methods of contraception during the study period and within 120 days after the end of the study, have a negative serological pregnancy test within 7 days prior to study enrollment, and must be non-lactating subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Proximal radical gastrectomy group; Patients with locally advanced upper gastric cancer were enrolled for 4 cycles of SOX combined with anti-PD-1 neoadjuvant therapy. After the completion of neoadjuvant therapy, the efficacy was evaluated, and the patients were divided into two groups according to the remission of lesions: (1) PD (Progressive disease) and SD (Stable disease) patients were replaced with conservative treatment or surgical treatment after MDT (Multi-disciplinary Treatment) discussion; (2) For PR (Partial response) and CCR (Clinical complete response) patients, if the patients met the criteria for proximal gastric radical surgery, the enrolled patients were randomly divided into 2 cohorts, which were divided into experimental group : the group of proximal gastric radical surgery; Four cycles of SOX combined with anti-PD-1 adjuvant therapy continued after surgery, and anti-PD-1 adjuvant therapy lasted for 1 year.	Procedure: Proximal radical gastrectomy; Proximal radical gastrectomy : Dissection of lymph nodes No.1,2,3a,4sa,4sb,7,8a, 9, 11p, 11dare recommended. The tumor involved more than 3cm of esophagus and additional dissection No.19, 20, 110. Gastrointestinal reconstruction method: double channel anastomosis is recommended, and other anastomosis methods can be carried out according to the surgeon's habit.
Active Comparator: Total radical gastrectomy group; Patients with untreated, operable locally advanced upper gastric cancer who signed informed consent and met the screening criteria were enrolled for 4 cycles of SOX combined with anti-PD-1 neoadjuvant therapy. After the completion of neoadjuvant therapy, the efficacy was evaluated, and the patients were divided into two groups according to the remission of lesions: (1) PD and SD patients were replaced with conservative treatment or surgical treatment after MDT discussion; (2) For PR and CCR patients, if the patients met the criteria for proximal gastric radical surgery, the enrolled patients were randomly divided into 2 cohorts, Cohort 2 (control group) : total radical gastrectomy group. Four cycles of SOX combined with anti-PD-1 adjuvant therapy continued after surgery, and anti-PD-1 adjuvant therapy lasted for 1 year.	Procedure: Total radical gastrectomy; total radical gastrectomy : Dissection of lymph nodes No.1-7, 8a, 9, 11p, 11d, 12a are recommended. The tumor involved more than 3cm of esophagus and additional dissection No.19, 20, 110. Gastrointestinal reconstruction method: Roux⁃en⁃Y anastomosis is recommended

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Disease-free survival (DFS)	DFS is based on RECIST(Response Evaluation Criteria in Solid Tumours) 1.1 as assessed by the investigator and is defined as the time from surgery initiation to the date of first documentation of disease recurrence or death due to any cause	UP to 3 years after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major pathologic response (MPR)	defined as the percentage of residual viable tumour cells in the tumour bed of no more than 10% after neoadjuvant therapy.	an average of 2 to 4 weeks after surgery
R0 resection rate	defined as the absence of tumor cells present at the resection margin under microscope	an average of 2 to 4 weeks after surgery
Overall Survival (OS)	defined as the time from randomization to death due to any cause.	UP to 5 years after surgery
Percentage of Participants Who Experience One or More Adverse Events (AEs)	An AE is based on NCI-CTC (The National Cancer Institute Common Toxicity Criteria) 5.0 as assessed by the investigator and is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience at least one AE will be presented.	Up to approximately 36 months
nutritional status	Nutrition was assessed with the patient-generated subjective global assessment (PG-SGA).	UP to 3 years after surgery
quality of life,EORTC QLQ-C30	Questionnaire includes EORTC QLQ-C30 (The European Organization for Reasearch and Treatment of Cancer Quality of Life Questionnare-Core 30))(version 3),	UP to 3 years after surgery

Collaborators and Investigators

• Sponsor: Guihua Wang
• Collaborators: Changhai Hospital; Xiangya Hospital of Central South University; Fudan University; First Affiliated Hospital, Sun Yat-Sen University; RenJi Hospital; Southwest Hospital, China; Qilu Hospital of Shandong University; First Affiliated Hospital Xi'an Jiaotong University; Ruijin Hospital; The First Affiliated Hospital of Zhengzhou University; Guangdong Provincial People's Hospital; The Third Xiangya Hospital of Central South University; Sixth Affiliated Hospital, Sun Yat-sen University; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai East Hospital; The First Affiliated Hospital of University of South China; First Hospital of China Medical University; General Hospital of Ningxia Medical University; Shanghai Changzheng Hospital; First Affiliated Hospital of Xinjiang Medical University; Southern Medical University, China; Yichang Central People's Hospital; Affiliated Hospital of Qinghai University; Xiangyang Central Hospital; Liaoning Cancer Hospital & Institute; The First Medical Center of Chinese PLA General Hospital; Shanxi Bethune Hospital; Jingzhou Central Hospital; Shandong First Medical University; The First Affilated Hospital of the Medical College, Shihezi University; People's Hospital of Macheng City; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: September 5, 2024
• First Submitted That Met QC Criteria: September 11, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; neoadjuvant chemotherapy; Locally advanced gastric cancer; Proximal radical gastrectomy; total radical gastrectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: 2024-S029

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: partial data will be shared 3 years after the study was completed and end in 5 years.
• IPD Sharing Access Criteria: A shared data acquisition scheme approved by the researcher
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No