Immunotherapy of Gastric Cancer With Autologous Tumor Derived Heat Shock Protein gp96

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of autologous gp96 treatment of gastric cancer.

Official Title
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Immunotherapy of Gastric Cancer With Autologous Tumor Derived Heat Shock Protein gp96

Conditions
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Gastric Carcinoma

Intervention / Treatment
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* Biological: autologous gp96 vaccination
* Drug: Oxaliplatin+S-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease characteristics: Histologically confirmed gastric carcinoma: clinical stage III (according to the Japanese gastric cancer classification), must have undergone radical resection Able to read and understand the informed consent document, must sign the informed consent Age: 18 to 75 years old Availability of at least 0.5 g tumor sample ECOG ≤1；life expectancy >=12 weeks, able to comply with study-related procedures Adequate bone marrow function including the absence of lymphopenia (ANC > 1,500/ mm3; Hemoglobin > 10g/dL ; platelet count >100,000/mm3), adequate liver function (serum glutamic oxaloacetic transaminase/ aspartate aminotransferase [AST], alanine amino transferase [ALT] <2.5 times institutional upper limit of normals [IULNs] and bilirubin (total) <1.5 times IULN), and adequate renal function (BUN and creatinine <1.5 times IULNs) Normal heart function NOT participate in ANY other clinical trials within 4 weeks prior to vaccination. Exclusion Criteria: Unable to get the informed consent Female patients who are pregnant or breastfeeding Progression prior to treatment as determined by the principal investigator Transplant recipient Patients currently diagnosed with Human Immunodeficiency Virus or other active uncontrolled infection Unstable or severe intercurrent medical conditions Patient with allergic constitution Patients with any systemic disease needed to be treated with immunosuppressant or Corticosteroids.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gp96 group<br>autologous gp96 vaccination + basal treatment for gastric cancer | Biological: autologous gp96 vaccination<br>* Vaccination of gp96 derived from autologous tumor tissue. Treatment will be started between 3-6 weeks after the surgery. gp96 of 25ug in 1mL normal saline s.c. on days 1 of each cycle, up to a maximum of 10 doses (1 cycle= 7 days). 200-400mg cyclophosphamide i.v. 1-3 days before each gp96 infusion.<br>Drug: Oxaliplatin+S-1<br>* Treatment will be start at the 5th week after the surgery. S-1: 40 60mg bid，d1 14 q3W; oxaliplatin:130mg/m2，iv drip for 2h，d1,q3W 6 cycles.<br>* Other names: Oxaliplatin(Sanofi-aventis), S-1(Taiho);|
| Other: control group<br>Oxaliplatin+S-1 | Drug: Oxaliplatin+S-1<br>* Treatment will be start at the 5th week after the surgery. S-1: 40 60mg bid，d1 14 q3W; oxaliplatin:130mg/m2，iv drip for 2h，d1,q3W 6 cycles.<br>* Other names: Oxaliplatin(Sanofi-aventis), S-1(Taiho);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival |  | 2 years | 
| Number of participants with adverse events related to gp96 immunotherapy | A complete blood count will be requested before the first vaccination, after the second vaccination and after the last vaccination to monitor the side effect of gp96 immunotherapy. And blood chemistries will also be requested at the same time point for the same reason. And other adverse events related to gp96 immunotherapy will be recorded according to the NCI-CTCAE 3.0 criteria. | participants will be followed from the day of the first vaccination to the 30th day after the last vaccination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in antigen specific T cells | Tumor antigen specific T cells will be determined by IFN-γ Enzyme-linked immunosorbent spot using the autologous tumor cell lysis as the antigen. | within 3 days before the first vaccination and within 3 days after the 10th vaccination | 
| Overall survival |  | 3 years |