The Conversion Therapy of Chemotherapy Plus Camrelizumab in Metastatic Gastric Cancer

Study Overview
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Brief Summary
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Gastric cancer is one of the most common malignant tumors of the digestive tract. Gastric cancer patients diagnosed for the first time in China have a higher proportion of advanced stages and a higher postoperative metastasis rate.Studies have shown that patients with good pathological response after preoperative neoadjuvant therapy (such as tumor regression grade, TRG0 or 1) have a better prognosis.The purpose of this study is to treat patients with advanced gastric cancer who are difficult to perform R0 surgery with chemotherapy combined with immunotherapy. At the same time as the primary cancerous lesions are reduced, the distant metastatic lesions are effectively controlled in order to perform R0 surgery and to improve the survival rate of patients with advanced gastric cancer.

Official Title
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A Single-arm, Multi-center, Prospective Clinical Study of Camrelizumab Combined With Chemotherapy Conversion Therapy for the Treatment of Unresectable Metastatic Gastric Cancer

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: Paclitaxel + S-1 + anti-PD-1 antibody (Peritoneal metastasis)
* Drug: SOX regimen + anti-PD-1 antibody (Liver metastasis, para-aortic lymph node metastasis )


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient voluntarily participates in the study with full informed consent and signs a written informed consent form. Age 18-75 years old, male or female. HER-2 negative unresectable gastric cancer. Patients with gastric cancer who PD-L1+（CPS≥1）or MSI-H/dMMR, or EBV（+）. According to the RECIST 1.1 assessment criteria, there is at least one measurable lesions. The expected survival time of the patient ≥ 12 weeks. ECOG 0-1. The patient has good organ function: no blood transfusion or colony stimulating factor and thrombopoietin have been received in the 14 days before the first study, neutrophil count ≥1.5×109/L, platelet count ≥80×109/ L hemoglobin ≥ 80 g/L, serum creatinine ≤ 1.5 times the upper limit of normal (ULN), total bilirubin ≤ 1.5 times the upper limit of normal (ULN), ALT, AST ≤ 2.5 times ULN (without liver metastasis) or ≤ 5 times ULN (such as liver metastasis occurred), albumin ≥30 g/L. Requirements for coagulation function: International normalized ratio (INR) ≤ 1.5 times ULN, prothrombin time (PT) ≤ 1.5 times ULN, activated partial thromboplastin time (aPTT) ≤ 1.5 times ULN. Requirements for electrolytes: the corrected serum calcium, blood potassium, and blood magnesium are within the normal range; Women of childbearing age are required to have a pregnancy test (serum or urine) within 7 days of entry and the results are negative and are willing to use appropriate methods of contraception during the trial and 8 weeks after the last drug is given. For men, it should be surgically sterilization or consent to the use of appropriate methods of contraception during the trial and 8 weeks after the last administration of the experimental drug. Exclusion Criteria: Those who are known to be allergic to the study drug or any of its excipients or have had severe allergic reactions. Patients who have received chemotherapy and monoclonal antibodies within 21 days and those who have received radiotherapy within 14 days. Participated in other clinical trials within 21 days before screening. Other malignant tumors have been diagnosed within 5 years before entering the study, except for skin basal cell carcinoma or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or intraductal carcinoma in situ of the breast that can be treated locally and cured . There is uncontrollable or symptomatic active central nervous system (CNS) metastasis, which can be manifested as clinical symptoms, cerebral edema, spinal cord compression, cancerous meningitis, leptomeningeal disease and/or progressive growth; imaging Prompt asymptomatic spinal cord compression, except for those who have been evaluated by specialists as stable and do not need treatment for the time being; For those who have received CNS metastasis treatment, imaging examinations during the screening period have shown that they have been stable for ≥4 weeks and have been stopped before the first study administration Except for systemic hormone therapy (prednisone or other curative hormones with a dose> 10 mg/day) for ≥ 4 weeks. Poorly controlled pleural effusion, abdominal effusion or pericardial effusion. Poorly controlled tumor-related pain; for patients who need analgesic treatment, they must receive a stable dose of treatment before participating in the study; should be suitable for palliative radiotherapy (for example, bone metastasis or metastasis that causes nerve damage) before enrollment. If appropriate, consider local treatment of asymptomatic metastatic lesions whose further growth may cause functional defects or intractable pain (for example, epidural metastases not related to spinal cord compression). Peripheral neuropathy or hearing loss ≥ 2 (according to NCI-CTCAE 5.0). Pregnant or (confirmed by blood or urine HCG test) or breastfeeding women, or subjects of childbearing age are unwilling or unable to take effective contraceptive measures (applicable to both male and female subjects) until after the last trial treatment at least 6 months. Patients with moderate to severe liver and kidney dysfunction. Diabetes that is difficult to control (refers to despite the large fluctuations in blood glucose under standard insulin treatment and frequent blood glucose monitoring, which affects the life of the patient and frequent hypotension).

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camrelizumab combined with chemotherapy<br>The enrolled patients will be administered in two ways according to the difference between peritoneal metastasis and liver metastasis | Drug: Paclitaxel + S-1 + anti-PD-1 antibody (Peritoneal metastasis)<br>* Drug：Paclitaxel 50mg/m², intravenous drip administration, d1, d8, q3w. Drug：Paclitaxel 20mg/m², intraperitoneal administration, d1, d8, q3w. Drug:S-1 Oral, d1-14, q3w. Drug:Camrelizumab 200mg，Intravenous drip administration, d1, q3w.<br>Drug: SOX regimen + anti-PD-1 antibody (Liver metastasis, para-aortic lymph node metastasis )<br>* Drug:Oxaliplatin Injection: 130mg/m² intravenous drip administration, d1, q3w. Drug:S-1 Oral, d1-14, q3w. Drug:Camrelizumab 200mg，Intravenous drip administration, d1, q3w.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | Defined as no residue under the microscope after resection | 6 months | 
| 2-year survival rate | Defined as the ratio of patients surviving two years after randomization. | 2-years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Defined as the proportion of patients whose tumors have shrunk to a certain degree and maintained for a certain period of time, including CR+PR. | 2 years | 
| Pathologic complete response | Defined as the number of people who have achieved complete pathological remission accounted for the proportion of people who met the plan. | 6 months | 
| Overall survival | Defined as the time from the start of randomization to the death of the patient. | 2 years |