Locally Advanced Gastric Cancer
Conditions
Keywords
Locally advanced gastric cancer, neoadjuvant chemotherapy, immunotherapy, Proximal radical gastrectomy, total radical gastrectomy
Brief summary
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
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.
Interventions
PROCEDUREProximal 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.
PROCEDURETotal 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
Sponsors
Guihua Wang
Fudan University
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Xiangya Hospital of Central South University
Shandong First Medical University
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
The First Medical Center of Chinese PLA General Hospital
Affiliated Hospital of Qinghai University
Qilu Hospital of Shandong University
Ruijin Hospital
First Affiliated Hospital, Sun Yat-Sen University
Southern Medical University, China
Shanxi Bethune Hospital
The First Affiliated Hospital of Zhengzhou University
The Third Xiangya Hospital of Central South University
Jingzhou Central Hospital
Xiangyang Central Hospital
Yichang Central People's Hospital
The First Affiliated Hospital of University of South China
Guangdong Provincial People's Hospital
People's Hospital of Macheng City
Southwest Hospital, China
Liaoning Cancer Hospital & Institute
RenJi Hospital
Changhai Hospital
The First Affilated Hospital of the Medical College, Shihezi University
First Affiliated Hospital Xi'an Jiaotong University
First Affiliated Hospital of Xinjiang Medical University
Sixth Affiliated Hospital, Sun Yat-sen University
First Hospital of China Medical University
Shanghai East Hospital
General Hospital of Ningxia Medical University
Shanghai Changzheng Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 3-year Disease-free survival (DFS) | UP to 3 years after surgery | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| major pathologic response (MPR) | an average of 2 to 4 weeks after surgery | defined as the percentage of residual viable tumour cells in the tumour bed of no more than 10% after neoadjuvant therapy. |
| R0 resection rate | an average of 2 to 4 weeks after surgery | defined as the absence of tumor cells present at the resection margin under microscope |
| Overall Survival (OS) | UP to 5 years after surgery | defined as the time from randomization to death due to any cause. |
| Percentage of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 36 months | 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. |
| nutritional status | UP to 3 years after surgery | Nutrition was assessed with the patient-generated subjective global assessment (PG-SGA). |
| quality of life,EORTC QLQ-C30 | UP to 3 years after surgery | Questionnaire includes EORTC QLQ-C30 (The European Organization for Reasearch and Treatment of Cancer Quality of Life Questionnare-Core 30))(version 3), |
Countries
China
Contacts
CONTACTGuihua Wang
CONTACTlisheng chen
Outcome results
None listed