| Eligibility |
Inclusion Criteria:
1. patients with a pathologically confirmed primary diagnosis of gastric/esophagogastric
junctional cancer who have not undergone chemotherapy, radiotherapy, or other
antitumor therapy prior to the start of the clinical trial;
2. age 18 to 75 years Eastern Coorperative Oncology Group (ECOG): 0 to 1 points;
3. diagnosis of metastatic adenocarcinoma of the peritoneum [peritoneal cancer index
(PCI) = 20 points] with or without ascites (beyond the pelvis but not reaching full
abdominal ascites) by laparoscopic exploration;
4. Voluntarily sign the informed consent form.
5. good cardiac function for resection with curative intent. If clinically indicated,
patients with underlying ischemic, valvular heart disease or other severe heart
disease should be evaluated preoperatively by a cardiologist;
6. normal function of major organs and subjects are required to meet the following
laboratory criteria: 1) Absolute neutrophil count (ANC) = 1.5x109/L in the last 14
days without granulocyte colony-stimulating factor (GCSF); 2) Platelets = 100 x 109/L
in the absence of blood transfusion in the last 14 days; 3) Hemoglobin > 9 g/dL
without transfusion or erythropoietin use in the last 14 days; 4) Total bilirubin =
1.5 x upper limit of normal (ULN); enrollment is also allowed if total bilirubin > 1.5
x ULN but direct bilirubin = ULN; 5) Aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) = 2.5 x ULN.
6) Blood creatinine =1.5×ULN and creatinine clearance (calculated using the Cockcroft-Gault
formula) =60 ml/min; 7) good coagulation function, defined as International Normalized
Ratio (INR) or Prothrombin Time (PT) = 1.5 x ULN; 8) Normal thyroid function, defined as
thyrotropin (TSH) within the normal range. If baseline TSH is outside the normal range,
subjects may also be enrolled if total T3 (or FT3) and FT4 are within the normal range; 9)
Cardiac enzyme profiles within the normal range (enrollment will be allowed if the
investigator determines that the laboratory abnormality is not of clinical significance);
7) Thyroid function: thyroid stimulating hormone (TSH) and free thyroxine (FT3/FT4) in the
normal range or mildly abnormal without clinical significance; 8. weight of 40 kg or more
(including 40 kg), or BMI > 18.5; 9. female patients must meet:
- Menopausal (defined as absence of menstruation for at least 1 year with no confirmed
cause other than menopause) status, or surgically sterilized (removal of ovaries
and/or uterus), or patients of childbearing potential must also meet the following
requirements:
- Pregnancy test within 7 days prior to first dose must be negative;
- Agree to use contraception with an annual failure rate of < 1% or remain abstinent
(avoid heterosexual intercourse) (at least 120 days from signing the informed consent
form until at least 9 months after the last dose of the test drug and at least 9
months after the procedure (contraceptive methods with an annual failure rate of < 1%
include bilateral tubal ligation, male sterilization, proper use of hormonal
contraceptives that suppress ovulation, hormone-releasing intrauterine contraceptives,
and copper-containing intrauterine devices). .;
- No breastfeeding is allowed. 10. The subject reads and fully understands the patient
instructions and signs the informed consent form.
Exclusion Criteria:
1. the patient has a previous (within 5 years) or concurrent other malignant tumor;
2. patients who are preparing for or have previously received organ or bone marrow
transplantation;
3. have had a blood transfusion within 2 weeks prior to the first dose, or have a history
of bleeding, and any bleeding event with a severity rating of 3 or more on the CTCAE
4.0 within 4 weeks prior to screening;
4. abnormal coagulation with bleeding tendency (INR in the absence of anticoagulants at
normal values > 1.5); patients treated with anticoagulants or vitamin K antagonists
such as warfarin, heparin, or their analogues; the use of low-dose warfarin (1 mg
orally once daily) for prophylactic purposes is permitted, provided the International
Normalized Ratio of the prothrombinogen time (INR) is = 1.5, or Small-dose aspirin (no
more than 100 mg daily);
5. an actinic/venous thrombotic event within 6 months prior to screening, such as
cerebrovascular accident (including transient ischemic attack), deep vein thrombosis
(except for venous thrombosis due to intravenous cannulation for pre-chemotherapy,
which has resolved in the judgment of the investigator), and pulmonary embolism;
6. myocardial infarction, poorly controlled arrhythmia (including QTc interval = 450 ms
in men and = 470 ms in women) within 6 months prior to the first dose (QTc interval is
calculated using the Fridericia formula);
7. the presence of NYHA class III-IV cardiac insufficiency or cardiac ultrasound: LVEF
(left ventricular ejection fraction) <50%;
8. urine protein =++ and confirmed 24-hour urine protein quantification >1.0 g;
9. have multiple factors that interfere with oral administration of medications (e.g.,
inability to swallow, chronic diarrhea, and intestinal obstruction)
10. pleural effusion with clinical symptoms requiring clinical intervention;
11. human immunodeficiency virus (HIV) infection;
12. active tuberculosis;
13. long-standing unhealed wounds or incompletely healed fractures;
14. patients with pre-existing and current interstitial pneumonitis, pneumoconiosis,
radiation pneumonitis, drug-associated pneumonitis, and severely impaired lung
function that may interfere with the detection and management of suspected
drug-associated pulmonary toxicity
15. the presence of a known active or suspected autoimmune disease, except those who are
in a stable state of that disease at the time of enrollment (not requiring systemic
immunosuppressive therapy);
16. a history of severe chronic autoimmune disease, such as systemic lupus erythematosus;
a history of inflammatory bowel disease, such as ulcerative enteritis, Crohn's
disease, or chronic diarrheal disease, such as irritable bowel syndrome; a history of
tuberculosis or tuberculosis; a history of active hepatitis B, hepatitis C, or HIV; or
well-controlled non-severe immune disorders, such as dermatitis, arthritis, or
psoriasis, may be eligible. .. Hepatitis B virus titers < 500copy/ml may be enrolled;
17. patients requiring treatment with systemic corticosteroids (> 10 mg/day prednisone
efficacy dose) or other immunosuppressive drugs within 14 days prior to the first dose
or during the study period. However, enrollment is permitted if patients are allowed
to use topical topical or inhaled steroids, or adrenal hormone replacement therapy at
doses = 10 mg/day prednisone efficacy dose in the absence of active autoimmune
disease;
18. any active infection requiring systemic administration of anti-infective therapy
within 14 days prior to the first dose; except for prophylactic antibiotic therapy
(e.g., for the prevention of urinary tract infections or chronic obstructive pulmonary
disease);
19. treatment with a live vaccine within 28 days prior to the first dose; except
inactivated viral vaccines for seasonal influenza;
20. prior treatment with antibodies/drugs targeting immune checkpoints, e.g., PD-1, PD-L1,
CTLA-4 inhibitors, etc;
21. have received treatment with immunologically-affecting related drugs or medical
technologies (including but not limited to the following: thymopentin, thymofacine,
interferon, CAR-T therapy, etc.) within 6 months prior to the first dose of the drug
22. is receiving treatment in another clinical study or is scheduled to begin treatment in
this study less than 1 month from the end of treatment in the previous clinical study;
23. has a known history of allergy or intolerance to any study medication or its
components
24. patients with a history of alcoholism, drug abuse, and substance abuse. Patients who
have stopped drinking alcohol may be enrolled;
25. patients with non-compliance with medical advice, non-adherence to prescribed
medication, or incomplete information that may affect the judgment of efficacy or
safety;
26. pregnant or lactating female patients;
27. patients with conditions that may increase the risk of study participation and study
medication, or other severe, acute, and chronic conditions that, in the judgment of
the investigator, make participation in a clinical study unsuitable.
28. other conditions that, in the judgment of the investigator, make them unsuitable for
this clinical trial.
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