Peri-operative Sintilimab in Combination With SOX in Locally Advanced Gastric Cancer

Tianjin Medical University

Status and phase: Enrolling; Phase 2

Conditions: Sintilimab; Perioperative; Gastric Cancer

Treatments: Drug: Oxaliplatin; Drug: Sintilimab; Drug: S-1

Study type: Interventional

Funder types: Other

Identifiers

NCT04982939

PERSIST

Details and patient eligibility

About

To evaluate efficacy and safety of peri-operative sintilimab in combination with SOX in resectable locally advanced gastric or gastroesophageal junction adenocarcinoma

Enrollment: 210 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female, 18 years old ≤ age ≤ 75 years old

• ECOG PS score 0-1

• Treatment naive patients diagnosed as gastric adenocarcinoma or gastroesophageal junction adenocarcinoma by histopathology

• No known HER2-positive status;

• Clinical stage Ⅱ, Ⅲ (T1-4a N+ M0, T3-4a N0 M0, AJCC 8th)

• The research center and the surgeon can complete D2 radical gastrectomy

• Physical condition and organ function allow for larger abdominal surgery

• Sufficient organ and bone marrow function, which is defined as follows:

  1. Blood routine: absolute neutrophil count (ANC)≥1.5×109/L; platelet count (PLT)≥100×109/L; hemoglobin content (HGB)≥9.0 g/dL.

  2. Liver function: Patients without liver metastasis require serum total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 ×ULN;

  3. Renal function: Creatinine clearance rate (Ccr) ≥50 mL/min (calculated by Cockcroft/Gault formula):

     1. Female: Ccr= (140-years old) x weight (kg) x 0.85/(72 x serum creatinine (mg/dL))
     2. Male: Ccr= (140-years old) x weight (kg) x 1.00/(72 x serum creatinine (mg/dL))

  4. The coagulation function is adequate, defined as the international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; if the subject is receiving anticoagulation therapy, as long as the PT is within the proposed range of anticoagulation drugs

• LVEF≥50%;

• Agree and be able to comply with the plan during the research period;

• Provide written informed consent before entering the study screening, and the patient has understood that participants can withdraw from the study at any time during the study without any loss;

Exclusion criteria

• Complicated with upper gastrointestinal obstruction/bleeding or abnormal digestive function or malabsorption syndrome;
• Complicated with severe uncontrolled concurrent infection or other severe uncontrolled concomitant disease, moderate or severe renal injury;
• Received previous anti-tumor therapy, including chemotherapy, radiotherapy, targeted therapy or immunotherapy, etc.;
• Suffered from other malignant tumors in the past 5 years (except basal cell or squamous cell carcinoma, superficial bladder cancer, cervical cancer in situ or breast cancer);
• Uncontrollable pleural effusion, pericardial effusion or ascites;
• Suffered from severe cardiovascular disease within 12 months before enrollment, such as symptomatic coronary heart disease, congestive heart failure ≥ Grade II, uncontrolled arrhythmia, and myocardial infarction;
• Allergic reactions to the drugs used in this study;
• Use steroids or other systemic immunosuppressive therapies 14 days before enrollment;
• Patients who received study drug treatment within 4 weeks before enrollment (participate in other clinical trials);
• Active autoimmune diseases;
• History of primary immunodeficiency;
• Have used immunosuppressive drugs within 4 weeks before the first dose of study treatment, excluding nasal spray, inhaled or other local glucocorticoids or physiological doses of systemic glucocorticoids (that is, no more than 10 mg/day Pred nisone or other glucocorticoids in equivalent doses), or use hormones to prevent allergy to contrast agents;
• Within 4 weeks before the first dose of study treatment or plan to receive live attenuated vaccine during the study period;
• Known to have active tuberculosis;
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
• HIV antibody positive, active hepatitis B or C (HBV, HCV);
• Pregnant or lactating women

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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210 participants in 2 patient groups

Experimental Group-Sintilimab in combination with SOX

Experimental group

Description:

Preoperative treatment: three cycles of sintilimab in combination with SOX. Radical gastrectomy and lymphadenectomy (D2). Postoperative treatment: five cycles of SOX, Sintilimab up to one year.

Treatment:

Drug: S-1

Drug: Oxaliplatin

Drug: Sintilimab

Active Comparator-SOX

Active Comparator group

Description:

Preoperative treatment: three cycles of SOX. Radical gastrectomy and lymphadenectomy (D2). Postoperative treatment: five cycles of SOX.

Treatment:

Drug: S-1

Drug: Oxaliplatin