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

Guihua Wang

Status and phase: Enrolling; Phase 4

Conditions: Locally Advanced Gastric Cancer

Treatments: Procedure: Proximal radical gastrectomy; Procedure: Total radical gastrectomy

Study type: Interventional

Funder types: Other

Identifiers

NCT06597227

2024-S029

Details and patient eligibility

About

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

Full 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.

Enrollment: 404 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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404 participants in 2 patient groups

Proximal radical gastrectomy group

Experimental group

Description:

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.

Treatment:

Procedure: Proximal radical gastrectomy

Total radical gastrectomy group

Active Comparator group

Description:

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.

Treatment:

Procedure: Total radical gastrectomy