Dynamic Multiomics Evaluation of Anti-HER2 and Immunotherapy in HER2 Positive Gastric Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Incidence rate of gene deletion, amplification, insertion and other types of variation of tumor evaluated by whole exon sequence(WES).
研究概览
简要总结
Dynamic multiomics explore the efficacy and mechanism of anti-HER2 & immunotherapy of HER2 Positive GC
详细描述
The investigators will recruit 100 HER2 positive advanced gastric 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 next-generation sequence , 10× genomics single-cell sequence ,whole exon sequence, proteome detection and CTC detection to explore the efficacy and mechanism of anti-HER2 & immunotherapy of HER2 positive GC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •* Having signed informed consent
- •* Age:18-80 years old
- •* HER2 overexpression confirmed by IHC or ISH (IHC 3+,or IHC2+/ISH+)
- •* Histologically confirmed gastric adenocarcinoma
- •* Unresectable recurrent or metastatic gastric cancer
- •* Previous neo-adjuvant or adjuvant treatment for gastric 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 \3,000/mm3, absolute neutrophil count ≥2000/mm3, platelet\>100,000/mm3, Hb\>9g/dl
排除标准
- •Previous systemic therapy for metastatic gastric 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
结局指标
主要结局
Incidence rate of gene deletion, amplification, insertion and other types of variation of tumor evaluated by whole exon sequence(WES).
时间窗: 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
DNA extracted from tumor tissue will be administrated to whole exon sequence.Variation features at treatment baseline, the second time point response and disease progression time point will be recorded and compared between two groups.
Proportions of HER2 & PD-L1 positive CTC
时间窗: 2 months
Numbers of CTC and proportions of HER2 or PD-L1 positive CTC collected at treatment baseline and every time point response will be calculated and recorded. Proportions of HER2 and PD-L1 positive CTC will be compared between two groups.
Tumor associated proteins expression level of tumor
时间窗: 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
96 tumor associated proteins' expression level of tumor at treatment baseline, second time point response and disease progression time point will be recorded and compared between two groups.
Incidence rate of ctDNA deletion, amplification, insertion and other types of variation evaluated by next generation sequence(NGS).
时间窗: 2 months
NGS will be proceeded to detect the ctDNA variations features at treatment baseline and every time point response will be recorded and compared between two groups.
Proportions of lymphocytes, stromal cells, tumor cells in tumor tissue assessed by single cell transcriptome sequence.
时间窗: 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
single cell digested from tumor tissue will be administrated to 10× genomics single cell transcriptome sequence. Proportions of lymphocytes, stromal cells, tumor cells assessed by single cell transcriptome sequence at treatment baseline, the second time point response and disease progression time point will be recorded and compared between two groups.
次要结局
未报告次要终点
研究者
Shen Lin
Professor
Peking University