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

April 20, 2022 updated by: Shen Lin, Peking University
Dynamic multiomics explore the efficacy and mechanism of anti-HER2 & immunotherapy of HER2 Positive GC

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100142
        • Recruiting
        • Beijing Cancer hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Anti-HER2 & Immunotherapy
Advancd gastric cancer patients received anti-HER2 & immunotherapy ± chemotherapy
Procedure: Samples including blood and tissue collection
Tissue and peripheral blood sample of 100 gastric cancer patients will be collected at the baseline and time point response of therapy.
Procedure: CTC detection
Peripheral blood collected from patients will be administrated to CTC detection.
Procedure: ctDNA detection
DNA extraction from patients' peripheral blood will be measured by 741 panel DNA sequence.
Procedure: 10×genomics single cell RNA sequence
Tissue collected from patients will be digested into single cell suspension and administrated to 10×genomics single cell RNA sequence.
Procedure: Whole exon sequence
DNA will be extracted from patients' tissue and administrated to whole exon sequence.
Procedure: Proteomics detection
Peripheral blood collected from patients will be administrated to proximity extension assay .
Other: Anti-HER2
Advancd gastric cancer patients received anti-HER2 ± chemotherapy.
Procedure: Samples including blood and tissue collection
Tissue and peripheral blood sample of 100 gastric cancer patients will be collected at the baseline and time point response of therapy.
Procedure: CTC detection
Peripheral blood collected from patients will be administrated to CTC detection.
Procedure: ctDNA detection
DNA extraction from patients' peripheral blood will be measured by 741 panel DNA sequence.
Procedure: 10×genomics single cell RNA sequence
Tissue collected from patients will be digested into single cell suspension and administrated to 10×genomics single cell RNA sequence.
Procedure: Whole exon sequence
DNA will be extracted from patients' tissue and administrated to whole exon sequence.
Procedure: Proteomics detection
Peripheral blood collected from patients will be administrated to proximity extension assay .

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportions of HER2 & PD-L1 positive CTC
Time Frame: 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.
2 months
Incidence rate of ctDNA deletion, amplification, insertion and other types of variation evaluated by next generation sequence(NGS).
Time Frame: 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.
2 months
Proportions of lymphocytes, stromal cells, tumor cells in tumor tissue assessed by single cell transcriptome sequence.
Time Frame: 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.
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
Incidence rate of gene deletion, amplification, insertion and other types of variation of tumor evaluated by whole exon sequence(WES).
Time Frame: 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.
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
Tumor associated proteins expression level of tumor
Time Frame: 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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2019

Primary Completion (Anticipated)

January 1, 2023

Study Completion (Anticipated)

January 1, 2025

Study Registration Dates

First Submitted

January 29, 2022

First Submitted That Met QC Criteria

April 20, 2022

First Posted (Actual)

April 27, 2022

Study Record Updates

Last Update Posted (Actual)

April 27, 2022

Last Update Submitted That Met QC Criteria

April 20, 2022

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CGOG-HER2-1001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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