Toripalimab Plus FLOT in Locally Advanced Gastric Cancer

Study Overview
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Brief Summary
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Neoadjuvant therapy for locally advanced gastric cancer is still in the exploratory stage. With the emergence of immune checkpoint inhibitors, neoadjuvant chemoimmunotherapy is also in the exploratory stage in locally advanced gastric cancer. At present, chemotherapy combined with immunotherapy is usually a simple combination of chemotherapeutic drugs and immune drugs, without taking into account of the influenece of applied sequence. The purpose of this study is to explore whether the sequence of chemotherapy and immunotherapy influence the complete pathological response rate in locally advanced gastric cancer.

Detailed Description
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Neoadjuvant therapy for locally advanced gastric cancer is still in the exploratory stage. With the emergence of immune checkpoint inhibitors, neoadjuvant chemoimmunotherapy is also in the exploratory stage in locally advanced gastric cancer. At present, chemotherapy combined with immunotherapy is usually a simple combination of chemotherapeutic drugs and immune drugs, without taking into account of the influenece of applied sequence. The purpose of this study is to explore whether the sequence of chemotherapy and immunotherapy influence the complete pathological response rate in locally advanced gastric cancer. All patients received toripalimab plus FLOT regimen. If pCR was achieved, the patients received two cycles of toripalimab plus FLOT, then toripalimab maintenance until one year, if pCR was not achieved, the patients received 8 cycles of perioperative toripalimab plus FLOT, then toripalimab maintenance until one year.

Official Title
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Toripalimab Combined With FLOT Regimen in Locally Advanced Gastric cancer-a Prospective, Open, Single-center, Phase Ⅱ Clinical Study

Conditions
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Chemotherapy, Immune Checkpoint Inhibitor, Locally Advanced Gastric Carcinoma

Intervention / Treatment
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* Drug: delayed toripalimab
* Drug: control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 70 ≥ Age ≥ 18 years regardless of gender Gastric adenocarcinoma confirmed by pathology no distant metastasis and resectable or potentially resectable evaluated by general surgery experts ECOG PS 0-1 clinical stage III by AJCC 8.0 expected lifespan over 3 months Adequate organ function: 1) without growth factor and blood component support in the first 2 weeks of enrollment; 2) Cardiac function: no heart disease or coronary heart disease, grade 1-2; 3) liver function: TBIL ≤ 2ULN, AST ≤ 2.5 ULN, alt ≤ 2.5 ULNX 4 Renal function: cr ≤ 1.25ULN, liver function: TBIL ≤ 2ULN, TBIL ≤ 2.5ULN, alt ≤ 2.5ULN, 4)renal function: cr ≤ 1.25ULN. blood pressure normal or controlled within the normal range by antihypertensive drugs Diabetic patients were treated with hypoglycemic drugs to control fasting blood glucose ≤ 8mmol/L Patients with positive hepatitis B surface antigen need to be tested for quantitative detection of hepatitis B DNA virus. HBV DNA should be less than the upper limit of the normal test value for patients with HBV infection. no other serious diseases conflicting with this study No history of other malignant tumors Women of childbearing age must be tested negative for blood pregnancy test within 7 days before enrollment, and subjects of childbearing age must use appropriate contraceptive measures during the trial and within 6 months after the trial agreement to participate in this study and signed the informed consent form Exclusion Criteria: Pregnant or lactating women Suffered from severe infectious diseases within 4 weeks before entering the group Bronchial asthma requires intermittent use of bronchodilators or medical intervention Due to the use of immunosuppressants before coexisting diseases and the dosage of immunosuppressants ≥ 10mg/, the oral dose of prednisone lasted for more than 2 weeks Clinically obvious cardio-cerebrovascular diseases, including, but not limited to, severe acute myocardial infarction, instability or severe angina pectoris, coronary artery bypass surgery, congestive heart failure, ventricular arrhythmias requiring medical intervention, left ventricular ejection fraction < 50%, stroke within 6 months Allergic to any experimental drug and its excipients, or have a history of severe allergy, or are contraindications to experimental drugs Severe mental disorders Abnormal coagulation function (PT > 16s, APTT > 53s, TT > 21s Fib < 1.5g/L), bleeding tendency or undergoing thrombolysis or anticoagulation therapy Past or present pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, severe impairment of lung function, etc. Unable to swallow research drugs, chronic diarrhea (including but not limited to irritable bowel syndrome, Crohn's disease, ulcerative colitis) and intestinal obstruction affect drug use and absorption Have a history of immunodeficiency, including positive for HIV, or suffer from other acquired, congenital immunodeficiency diseases, or have a history of organ transplant Other researchers evaluate those who do not meet the criteria for admission

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: patients were randomized at 1:1 into experiment group and control group. In control group patients received chemotherapy and toripalimab on same day, in experiment group patients received chemotherapy on day 1 and toripalimab on day 3.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>patients received FLOT regimen on day 1 and toripalimab on day 3. | Drug: delayed toripalimab<br>* chemotherapy plus toripalimab and toripalimab was delayed on day 3. If the pCR was not achieved after surgery, then the patients received five cycles of FLOT plus toripalimab every two weeks, then toripalimab maintenance until one year. If pCR was achieved, then then the patients received two cycles of original regimen and then toripalimab maintenance until one year.<br>* Other names: experiment group;|
| Other: control group<br>patients received FLOT regimen and toripalimab on day 1. | Drug: control<br>* chemotherapy and toripalimab were given on same day. If the pCR was not achieved after surgery, then the patients received four cycles of FLOT plus toripalimab every two weeks, then toripalimab maintenance until one year. If pCR was achieved, then then the patients received two cycles of original regimen and then toripalimab maintenance until one year.<br>* Other names: control group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathological complete response rate | the proportion of patients with no tumor cells in the postoperative specimens | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of adverse events | rate of adverse events | 3 months | 
| disease-free survival | the rate of patients who keep from disease at three years | 3 years |