Prospectively Predict the Efficacy and Explore the Mechanism of Treatment of Gastrointestinal Tumors Based on Peripheral Multi-omics Liquid Biopsy

Study Overview
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Brief Summary
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Dynamic multiomics detection of plasma derived exosomes to explore the efficacy and mechanism of anti-HER2, immunotherapy and anti-CLDN18.2 of gastrointestinal cancer.

Detailed Description
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The investigators will recruit 500 advancer/late-stage gastrointestinal cancer patients.Blood and tumor tissue will be collected at treatment baseline, every time point response till disease progression. All samples will be processed by exosomes proteome detection to explore the efficacy and mechanism of anti-HER2, immunotherapy and anti-CLDN18.2 of gastrointestinal cancer.

Official Title
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A Clinical Study Initiated by Investigator:Prospectively Predict the Efficacy and Explore the Mechanism of Precise Treatment of Gastrointestinal Tumors Based on Peripheral Blood Multi- Omics Liquid Biopsy

Conditions
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Advanced or Late Stage Gastrointestinal Cancer

Intervention / Treatment
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* Device: EV-array detection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Having signed informed consent Age:18-80 years old Histologically confirmed GI cancer Unresectable recurrent or metastatic GI cancer Previous neo-adjuvant or adjuvant treatment for GI cancer, if applicable, more than 6 months Measurable disease according to the RECIST criteria Karnofsky performance status ≥70 Life expectancy of ≥3 month No prior radiotherapy except radiotherapy at non-target lesion of the study more than 4 weeks ALT and AST<2.5 times ULN (≤5 times ULN in patients with liver metastases) Serum albumin level ≥3.0g/dL Serum AKP < 2.5 times ULN Serum creatinine <ULN, and CCr < 60ml/min Bilirubin level < 1.5 ULN WBC>3,000/mm3, absolute neutrophil count ≥2000/mm3, platelet>100,000/mm3, Hb>9g/dl Exclusion Criteria: Previous systemic therapy for metastatic GI cancer Surgery (excluding diagnostic biopsy) within 4 weeks prior to study entry Contraindications of nuclear magnetic resonance image such as fitment of cardiac pacemaker , nerve stimulator, or aneurysm clip, and metallic foreign body in eye ball and so on. Allergic constitution or allergic history to protium biologic product or any investigating agents. Severe heart disease or such history as recorded congestive heart failure, uncontrolled cardiac arrhythmia, angina pectoris needing medication, cardiac valve disease, severe abnormal ECG findings, cardiac infarction , or retractable hypertension. Pregnancy or lactation period Other previous malignancy within 5 year, except non-melanoma skin cancer Legal incapacity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gastrointestinal cancer (GI) patients receiving immunotherapy<br> | Device: EV-array detection<br>* Collect peripheral blood sample of 500 GI patients at treatment baseline, every time point response till disease progression.Blood samples will be transferred to central lab to detect certain exosome proteins expression by EV-array.Tumor response evaluation will be performed after two cycles of therapy by CT/MRI based on RECIST.Clinical data, including tumor stage,metastatic organ ,regimen, objective response, progression free survival, overall survival, etc, will be collected according to study protocol.<br>|
| GI patients receiving anti-HER2 therapy<br> | Device: EV-array detection<br>* Collect peripheral blood sample of 500 GI patients at treatment baseline, every time point response till disease progression.Blood samples will be transferred to central lab to detect certain exosome proteins expression by EV-array.Tumor response evaluation will be performed after two cycles of therapy by CT/MRI based on RECIST.Clinical data, including tumor stage,metastatic organ ,regimen, objective response, progression free survival, overall survival, etc, will be collected according to study protocol.<br>|
| GI patients receiving anti-CLDN18.2 therapy<br> | Device: EV-array detection<br>* Collect peripheral blood sample of 500 GI patients at treatment baseline, every time point response till disease progression.Blood samples will be transferred to central lab to detect certain exosome proteins expression by EV-array.Tumor response evaluation will be performed after two cycles of therapy by CT/MRI based on RECIST.Clinical data, including tumor stage,metastatic organ ,regimen, objective response, progression free survival, overall survival, etc, will be collected according to study protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor associated proteins expression level of exosomes | 90 tumor associated proteins' expression level of plasma derived exosomes at treatment baseline, second time point response and disease progression time point will be recorded. | Treatment baseline; Up to 2 months from the initial treatment; From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months |