Overview

Efficacy of Perioperative Chemotherapy Plus PD-1 Antibody in the Locally Advanced Gastric Cancer

Status:
Recruiting
Trial end date:
2024-10-05
Target enrollment:
0
Participant gender:
All
Summary
For locally advanced gastric cancer (cT3-4aN+M0), neoadjuvant chemotherapy can downstage T and N stage, increase the resectability of tumor, and finally improve the long-term survival. Combination of perioperative PD-1 antibody and chemotherapy for locally advanced gastric cancer could be a novel therapy to increase response rate and resectability and reduce recurrence rate. JS001 in this study is a Chinese anti-PD-1 monoclonal antibody for injection which has been approved for melanoma. This study is a multi-center, open-label, randomized phase II clinical trial to evaluate tolerability, safety and efficacy of JS001 in combination with perioperative chemotherapy in locally advanced gastric cancer.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Sun Yat-sen University
Collaborator:
Shanghai Junshi Bioscience Co., Ltd.
Treatments:
Antibodies
Capecitabine
Immunoglobulins
Oxaliplatin
Criteria
Inclusion Criteria:

1. Written (signed) informed consent;

2. Histologically CT/MRI confirmed cT3-4aN+M0 gastric adenocarcinoma;

3. Consent to send tumor tissue from biopsy or resection for PD-L1, EBV, MSI detection;

4. Female or male, 18-75 years;

5. ECOG 0-1, no surgery contraindications;

6. Physical condition and adequate organ function to ensure the success of abdominal
surgery;

7. Expected survival ≥3 months;

8. Adequate hematological, liver, renal and coagulation function;

1) Platelet (PLT) count ≥100,000 /mm3; 2) Neutrophil count (ANC) ≥1,500 /mm3; 3) Hemoglobin
(Hb) level ≥9.0 g/dl; 4) International normalized ratio (INR) ≤1.5; 5) Prothrombin time
(PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN; 6) Glycosylated hemoglobin
(HbA1c) <7.5%; 7) Total bilirubin (TBIL) level ≤1.5×ULN; 8) Alanine aminotransferase (ALT)
and aspartate aminotransferase (AST) level ≤2.5×ULN (≤5×ULN in case of liver metastasis);
9) Alkaline phosphatase level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 10) Serum
creatinine (Cr) level ≤1.5×ULN and creatinine clearance ≥60 ml/min; 11) Thyroid stimulating
hormone (TSH) ≤ULN; 12) Normal serum free thyroid hormone (T4); 13) Normal serum free
triiodothyronine (T3); 14) Serum amylase ≤1.5×ULN; 15) Lipase ≤1.5×ULN.

9.Females of child bearing age must have a negative pregnancy test, and have to take
contraception measures and avoid breast feeding during the study and for 3 months after the
last dose; male subjects must agree to taken contraception measures during the study and
for 3 months after the last dose.

Exclusion Criteria:

1. Known allergy to study drug or excipients, or allergy to similar drugs;

2. Patients with active malignant tumor in recent 2 years, except the tumor studied in
this research or cured localized tumor like resected basal cell or squamous cell skin
cancer, superficial bladder cancer, cervical or breast carcinoma in situ;

3. Uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before
recruitment;

4. Weight loss >20% within 2 weeks before recruitment;

5. Unable to swallow study drug;

6. Prior chemotherapy, radiotherapy, surgery for gastric cancer;

7. Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent;

8. Prior therapy with tyrosine kinase inhibitor within 2 weeks.

9. Concurrent medical condition requiring the use of cortisol (>10mg/day Prednisone or
equivalent dose) or other systematic immunosuppressive medications within 14 days
before the study treatment. Except: inhalation or topical corticosteroids. Doses > 10
mg/day prednisone or equivalent for replacement therapy;

10. Have vaccination with attenuated live vaccines within 4 weeks prior to initiation of
the study treatment or plan to vaccinate during the study;

11. Poorly controlled hypertension or diabetes;

12. With bleeding tendency, or evident hemoptysis or other hemorrhagic events (e.g.
gastrointestinal hemorrhage, hemorrhagic gastric ulcer) within 2 months prior to
initiation of study treatment, or presence of hereditary or acquired bleeding or
thrombotic tendency (e.g. hemophilia, coagulopathy, thrombocytopenia, etc.), or
current/long-term thrombolytic or anticoagulant therapy (except aspirin ≤100 mg/day);

13. Present or history of any autoimmune disease;

14. With active tuberculosis or receiving previous anti-tuberculosis therapy within one
year;

15. Diagnosed with interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis,
acute lung disease;

16. Pregnancy or breast feeding;

17. Human immunodeficiency virus (HIV) infection (HIV antibody positive), or active
hepatitis C virus (HCV) infection (HCV antibody positive), or active hepatitis B virus
(HBV) infection (HBsAg or HBcAb positive, and HBV-DNA ≥2000 IU/ml (copies/ml)), or
other severe infection requiring systemic antibiotic treatment, or unexplained body
temperature >38.5℃ during screening period/before study treatment;

18. Patients with other severe acute or chronic conditions that may increase the risk of
participation in the study and study treatment, or may interfere with interpretation
of study results, and judged by the investigator as not suitable for participation in
this clinical trial.