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

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

Official Title
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Efficacy and Safety of Peri-operative Sintilimab in Combination With SOX in Resectable Locally Advanced Gastric Cancer: a Multiple-center Open-label Randomized Phase II Trial.

Conditions
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Gastric Cancer, Perioperative, Sintilimab

Intervention / Treatment
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* Drug: Sintilimab
* Drug: S-1
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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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: Blood routine: absolute neutrophil count (ANC)≥1.5×109/L; platelet count (PLT)≥100×109/L; hemoglobin content (HGB)≥9.0 g/dL. 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; Renal function: Creatinine clearance rate (Ccr) ≥50 mL/min (calculated by Cockcroft/Gault formula): Female: Ccr= (140-years old) x weight (kg) x 0.85/(72 x serum creatinine (mg/dL)) Male: Ccr= (140-years old) x weight (kg) x 1.00/(72 x serum creatinine (mg/dL)) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group-Sintilimab in combination with SOX<br>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. | Drug: Sintilimab<br>* Sintilimab, 200mg IV d1 Q3W<br>* Other names: IBI308;Drug: S-1<br>* S-1, 40-60mg BID d1-14 Q3W<br>Drug: Oxaliplatin<br>* Oxaliplatin，130mg/m2 d1 Q3W<br>|
| Active Comparator: Active Comparator-SOX<br>Preoperative treatment: three cycles of SOX. Radical gastrectomy and lymphadenectomy (D2). Postoperative treatment: five cycles of SOX. | Drug: S-1<br>* S-1, 40-60mg BID d1-14 Q3W<br>Drug: Oxaliplatin<br>* Oxaliplatin，130mg/m2 d1 Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological complete response (pCR) rate | Pathological complete response (pCR) rate is defined as the proportion of participants whose tumor in the stomach and lymph node completely disappeared, as determined by a pathologist. | up to 8 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor down-staging rate | Tumor down-staging is defined as any stage reduction between clinical and pathologic stage | up to 8 weeks after surgery | 
| Major pathological response (MPR) rate | Major pathological response (MPR) rate is defined as the proportion of participants whose percentage of residual tumor in the stomach and lymph node decreased to < 10%, as determined by a pathologist. | up to 8 weeks after surgery | 
| 3 years disease-free survival (DFS) rate | 3 years disease-free survival (DFS) rate is defined as proportion of participants who have no recurrence or metastasis after 3 years of radical treatment | up to 4 years | 
| 5 years overall survival (OS) rate | 5 years overall survival (OS) rate is defined as proportion of participants who survived 5 years after radical treatment | up to 6 years | 
| Adverse event | All grades of adverse events, all grades of treatment related adverse events, serious of adverse events | up to 30 days after last treatment administration | 
| Overall response rate ( ORR) | Overall response rate ( ORR) is defined as proportion of participants who have a best response of CR or PR | up to 30 days after last preoperative treatment administration | 
| Disease Control Rate (DCR) | Disease Control Rate (DCR) is defined as proportion of participants who have a best response of CR、PR or SD | up to 30 days after last preoperative treatment administration |