Concurrent Chemoradiotherapy Combined With Sintilimab as Neoadjuvant Therapy for Advanced Gastric Cancer Patients With Para-aortic Lymph Node Metastasis: a Single-arm, Phase II, Exploratory Study.
This trial is a prospective, single arm, single center, phase II clinical study aimed at subjects with advanced gastric cancer and para aortic lymph node metastasis, exploring the feasibility and safety of Sintilimab Injection combined with synchronous chemo-radiotherapy as neoadjuvant therapy. Patients will receive sintilimab Injection (200mg iv q3w d1) combined with concurrent radiotherapy and chemotherapy. The chemotherapy regimen will use oxaliplatin 130mg/m2+S-1 40mg/m2 bid d1-14. Radiotherapy is performed using intraperitoneal radiation therapy, once a day, five times a week, at a dose of 1.8-2 Gy/f, for a total of 45-50.4 Gy (60-66 Gy for lymph node lesions). Radiation therapy starts from the second cycle of Sintilimab Injection combined with chemotherapy. The subjects underwent imaging evaluation after completing 4 cycles of combination chemotherapy and radiation therapy with Sintilimab Injection. Evaluated as a surgical subject (surgical conditions: imaging evaluation of enlarged lymph nodes adjacent to the abdominal aorta with PR or no significant activity), radical surgery will be performed within 4 weeks after the last study drug treatment. After surgery, the researcher will determine the necessity of adjuvant treatment and develop an adjuvant treatment plan based on the subject's condition. Subjects evaluated as inoperable will have their best follow-up treatment plan determined by the researcher.
• Able to provide informed consent and willing to sign an approved consent form;
• age ≥ 18 years old and ≤ 75 years old, male and female;
• Has histologically confirmed diagnosis of gastric or GEJ adenocarcinoma;
• patients with advanced gastric cancer who have para aortic lymph node metastasis at the initial treatment and whose primary tumor site can be treated with D2 radical operation;
• peritoneal exploration to exclude peritoneal metastasis, liver metastasis and other metastasis;
• CT or MRI, PET-CT and other examinations suggest that there is only one unresectable factor, namely, para aortic lymph node metastasis;
• has not receive previous anti-tumor treatment (radiotherapy, chemotherapy, targeted or immunotherapy, etc.);
• Has at least one measurable lesion as defined by RECIST 1.1 as determined by investigator assessment.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• expected survival time \>3 months;
• sufficient organ function, the subject needs to meet the following laboratory indicators:
‣ The absolute neutrophil count (ANC) ≥ 1.5x109/l without granulocyte colony stimulating factor in the past 14 days.
⁃ Platelets ≥ 100 without blood transfusion in recent 14 days × 109/l.
⁃ Hemoglobin \>9g/dl without blood transfusion or use of erythropoietin in recent 14 days;
⁃ Total bilirubin ≤ 1.5 × Upper limit of normal value (ULN);
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were ≤ 2.5 × ULN (ALT or AST ≤ 5 allowed for subjects with liver metastasis × ULN);
⁃ Blood creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by Cockcroft Gault formula) ≥ 60 ml/min;
⁃ Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;
⁃ Thyroid function was normal, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test at the timing of enrollment. Women of non-childbearing potential was defined as having a cessation of menses for one or more year or having surgical sterilization/Hysterectomy
• Participants of childbearing potential must be willing to use an adequate method of contraception （method with failure rate less than 1% in a year）for the course of the study through 120 days after the last dose of study medication or through 180 days of last dose of chemotherapy.