| Eligibility |
Inclusion Criteria:
1. Histologically or cytologically confirmed adenocarcinoma involving the
gastroesophageal junction or gastric cardia.
2. Having an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 7
days before enrollment.
3. Being histologically diagnosed with adenocarcinoma.
4. Having tumor lesions at stomach or gastroesophageal junction (Siewert type II or III);
5. Clinically diagnosed stage T1-2N+M0/T3-T4aNanyM0 according to ultrasound endoscopy or
enhanced CT/MRI scan.
6. At least one evaluable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
7. Surgical consultation at enrolling site to confirm that patient will be able to
undergo curative resection after completion of neoadjuvant therapy =< 56 days prior to
registration.
8. Physical condition and adequate organ function to ensure the success of abdominal
surgery.
9. Adequate hematological function: Neutrophil count = 1.5 × 109/L, Platelets = 100 ×
109/L and Hemoglobin =90g/L.
10. Adequate liver function: Total bilirubin = 1.5 × upper limit of normal (ULN); AST
(SGOT) and ALT (SGPT) < 2.5 × ULN in the absence of liver metastases, or < 5 × ULN in
case of liver metastases. ALP = 2.5 × upper limit of normal (ULN); ALB =30g/L.
11. Adequate renal function: Serum creatinine = 1.5 x ULN, and creatinine clearance = 60
ml/min.
12. Adequate coagulation function: INR/PT= 1.5 x ULN, aPTT= 1.5 x ULN.
13. No serious concomitant disease that will threaten the survival of patients to less
than 5 years.
14. Male or female. Age = 18 years and =80 years.
15. Written (signed) informed consent.
16. Good compliance with the study procedures, including lab and auxiliary examination and
treatment.
17. Female patients should not be pregnant or breast feeding.
18. Female patients of childbearing potential must be willing to use 2 methods of birth
control or be surgically sterile, or abstain from heterosexual activity for the course
of the study through 120 days after the last dose of study medication.
Exclusion Criteria:
1. Patients with distant metastasis or unresectable primary lesion.
2. Received prior treatment or receiving current treatment for this malignancy.
3. Patients who have digestive tract bleeding in 2 weeks before recruitment or with high
risk of bleeding.
4. Perforation / fistula of GI tract in 6 months before recruitment.
5. Patients with upper GI tract obstruction or functional abnormality or malabsorption
syndrome, which can affect absorption of apecitabine.
6. Patients with active autoimmune disease or history of refractory autoimmune disease.
7. Patients with active malignant tumor in recent 2 years, except the tumor studied in
this research or cured locally tumor like resected basal cell or squamous cell skin
cancer, superficial bladder cancer, cervical or breast carcinoma in situ.
8. Uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before
recruitment.
9. Pulmonary disease history: interstitial pulmonary disease, non-infective pneumonitis,
pulmonary fibrosis, acute pulmonary disease.
10. Uncontrollable systemic diseases, including diabetes, hypertension, etc.
11. Severe chronic or active infections in need of systemic antibacterial, antifungal, or
antiviral treatment, including TB or HIV, etc.
12. Patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml or positive HCV
RNA.
13. Patients with any cardiovascular risk factors below:
1. cardiac chest pain occurring in 28 days before recruitment, defined as moderate
pain that limits daily activity.
2. pulmonary embolism with symptoms occurring in 28 days before recruitment.
3. acute myocardial infarction occurring in 6 months before recruitment.
4. any history of heart failure reaching grade 3/4 of NYHA in 6 months before
recruitment.
5. ventricular arrhythmias of Grade 2 or grater in 6 months before recruitment, or
accompanied by supraventricular tachyarrhythmias requiring medical treatment.
6. cerebrovascular accident within 6 months before recruitment.
14. Moderate or severe renal injury [creatinine clearance rate=50 ml/min (according to
Cockroft & Gault equation)], or Scr>ULN.
15. Dipyrimidine dehydrogenase (DPD) deficiency.
16. Allergic to any drug in this study.
17. History of allogeneic stem cell transplantation or organ transplantation.
18. Use of steroids (dosage>10mg/d prednisone) or other systemic immune suppressive
therapy in 14 days before recruitment, except patients treated with regimens below: a.
steroids for hormone replacement (dosage>10mg/d prednisone); b. steroids for local
application with little systemic absorption; c. short -term (= 7 days) steroids for
preventing allergy or vomiting.
19. Vaccinated with live vaccine in 4 weeks before recruitment.
20. Receiving immune (interleukin, interferon, thymin) treatment or treatment of other
trials in 28 days before recruitment.
21. Receiving palliative radiation in 14 days before recruitment.
22. History of anti PD-1, PD-L1, PD-L2 or any other specific T cell co-stimulation or
checkpoint pathway targeted treatment.
23. Patients who lose =20% of body weight within 2 months before enrollment.
24. For patients with uncontrolled epilepsy, CNS diseases or history of mental disorder,
researchers should evaluate whether their diseases will impede their signing of
informed consent or compliance of treatment.
25. Existing of potential situation which will impede drug administration or affect
toxicity analysis or alcohol/ drug abuse.
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