Dynamic Multiomics Evaluation of Anti-HER2 and Immunotherapy in HER2 Positive Gastric Cancer

Not Applicable

Recruiting

• Conditions: HER2 Positive Advanced Gastric Cancer
• Interventions: Procedure: Samples including blood and tissue collection; Procedure: CTC detection; Procedure: ctDNA detection; Procedure: 10×genomics single cell RNA sequence; Procedure: Whole exon sequence; Procedure: Proteomics detection

• Registration Number: NCT05348161
• Lead Sponsor: Peking University

Brief Summary

Dynamic multiomics explore the efficacy and mechanism of anti-HER2 \& immunotherapy of HER2 Positive GC

Detailed Description

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.

Study Timeline

• Study Start: 2019-01-01
• Status Verified: 2021-12
• Study First Submitted: 2022-01-29
• Study First Submitted QC: 2022-04-20
• Last Update Submitted: 2022-04-20
• Study First Posted: 2022-04-27
• Last Update Posted: 2022-04-27
• Primary Completion: 2023-01-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• 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 <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 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anti-HER2 & Immunotherapy	CTC detection	Advancd gastric cancer patients received anti-HER2 \& immunotherapy ± chemotherapy
Anti-HER2	Proteomics detection	Advancd gastric cancer patients received anti-HER2 ± chemotherapy.
Anti-HER2 & Immunotherapy	ctDNA detection	Advancd gastric cancer patients received anti-HER2 \& immunotherapy ± chemotherapy
Anti-HER2 & Immunotherapy	Proteomics detection	Advancd gastric cancer patients received anti-HER2 \& immunotherapy ± chemotherapy
Anti-HER2	CTC detection	Advancd gastric cancer patients received anti-HER2 ± chemotherapy.
Anti-HER2	10×genomics single cell RNA sequence	Advancd gastric cancer patients received anti-HER2 ± chemotherapy.
Anti-HER2	Whole exon sequence	Advancd gastric cancer patients received anti-HER2 ± chemotherapy.
Anti-HER2	ctDNA detection	Advancd gastric cancer patients received anti-HER2 ± chemotherapy.
Anti-HER2 & Immunotherapy	Samples including blood and tissue collection	Advancd gastric cancer patients received anti-HER2 \& immunotherapy ± chemotherapy
Anti-HER2 & Immunotherapy	10×genomics single cell RNA sequence	Advancd gastric cancer patients received anti-HER2 \& immunotherapy ± chemotherapy
Anti-HER2 & Immunotherapy	Whole exon sequence	Advancd gastric cancer patients received anti-HER2 \& immunotherapy ± chemotherapy
Anti-HER2	Samples including blood and tissue collection	Advancd gastric cancer patients received anti-HER2 ± chemotherapy.

Primary Outcome Measures

Name	Time	Method
Incidence rate of gene deletion, amplification, insertion and other types of variation of tumor evaluated by whole exon sequence(WES).	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	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	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).	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.	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.

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China