Clinical trial NCT06597227: Proximal Gastrectomy Vs Total Gastrectomy in Locally Advanced Upper Gastric Cancer After Neoadjuvant Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Locally Advanced Gastric Cancer
Keywords: Locally advanced gastric cancer
neoadjuvant chemotherapy
immunotherapy
Proximal radical gastrectomy
total radical gastrectomy
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: Fudan University
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: The First Affiliated Hospital of Air Force Medicial University
name: Xiangya Hospital of Central South University
name: The First affiliated Hospital of Shandong Second Medical University
name: Wuhan Union Hospital, China
name: The First Medical Center of Chinese PLA General Hospital
name: Affiliated Hospital of Qinghai University
name: Qilu Hospital of Shandong University
name: Ruijin Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: Southern Medical University, China
name: Zhongnan Hospital
name: Shanxi Bethune Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Fujian Medical University Union Hospital
name: The Third Xiangya Hospital of Central South University
name: Jingzhou Central Hospital
name: Xiangyang Central Hospital
name: Yichang Central People's Hospital
name: People's Hospital of Macheng City
name: The First Affiliated Hospital of University of South China
First posted: 2024-09-19
Enrollment: 404
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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:

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  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.

Primary outcomes:
measure: 3-year Disease-free survival (DFS)
timeFrame: UP to 3 years after surgery
Secondary outcomes:
measure: major pathologic response (MPR)
timeFrame: an average of 2 to 4 weeks after surgery
measure: R0 resection rate
timeFrame: an average of 2 to 4 weeks after surgery
measure: Overall Survival (OS)
timeFrame: UP to 5 years after surgery
measure: Percentage of Participants Who Experience One or More Adverse Events (AEs)
timeFrame: Up to approximately 36 months
measure: nutritional status
timeFrame: UP to 3 years after surgery
measure: quality of life
timeFrame: UP to 3 years after surgery
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital, Huazhong University of Science and Technology
state: Hubei
Study officials:
References: