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

Primary Purpose

HER2 Positive Advanced Gastric Cancer

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Samples including blood and tissue collection
CTC detection
ctDNA detection
10×genomics single cell RNA sequence
Whole exon sequence
Proteomics detection
Sponsored by
Peking University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional screening trial for HER2 Positive Advanced Gastric Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Beijing Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Anti-HER2 & Immunotherapy

Anti-HER2

Arm Description

Advancd gastric cancer patients received anti-HER2 & immunotherapy ± chemotherapy

Advancd gastric cancer patients received anti-HER2 ± chemotherapy.

Outcomes

Primary Outcome Measures

Proportions of HER2 & PD-L1 positive CTC
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.
Incidence rate of ctDNA deletion, amplification, insertion and other types of variation evaluated by next generation sequence(NGS).
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.
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.
Incidence rate of gene deletion, amplification, insertion and other types of variation of tumor evaluated by whole exon sequence(WES).
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.
Tumor associated proteins expression level of tumor
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.

Secondary Outcome Measures

Full Information

First Posted
January 29, 2022
Last Updated
April 20, 2022
Sponsor
Peking University
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1. Study Identification

Unique Protocol Identification Number
NCT05348161
Brief Title
Dynamic Multiomics Evaluation of Anti-HER2 and Immunotherapy in HER2 Positive Gastric Cancer
Official Title
Dynamic Multiomics Evaluation of Anti-HER2 and Immunotherapy in HER2 Positive Gastric Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2019 (Actual)
Primary Completion Date
January 1, 2023 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HER2 Positive Advanced Gastric Cancer

7. Study Design

Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Anti-HER2 & Immunotherapy
Arm Type
Other
Arm Description
Advancd gastric cancer patients received anti-HER2 & immunotherapy ± chemotherapy
Arm Title
Anti-HER2
Arm Type
Other
Arm Description
Advancd gastric cancer patients received anti-HER2 ± chemotherapy.
Intervention Type
Procedure
Intervention Name(s)
Samples including blood and tissue collection
Intervention Description
Tissue and peripheral blood sample of 100 gastric cancer patients will be collected at the baseline and time point response of therapy.
Intervention Type
Procedure
Intervention Name(s)
CTC detection
Intervention Description
Peripheral blood collected from patients will be administrated to CTC detection.
Intervention Type
Procedure
Intervention Name(s)
ctDNA detection
Intervention Description
DNA extraction from patients' peripheral blood will be measured by 741 panel DNA sequence.
Intervention Type
Procedure
Intervention Name(s)
10×genomics single cell RNA sequence
Intervention Description
Tissue collected from patients will be digested into single cell suspension and administrated to 10×genomics single cell RNA sequence.
Intervention Type
Procedure
Intervention Name(s)
Whole exon sequence
Intervention Description
DNA will be extracted from patients' tissue and administrated to whole exon sequence.
Intervention Type
Procedure
Intervention Name(s)
Proteomics detection
Intervention Description
Peripheral blood collected from patients will be administrated to proximity extension assay .
Primary Outcome Measure Information:
Title
Proportions of HER2 & PD-L1 positive CTC
Description
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.
Time Frame
2 months
Title
Incidence rate of ctDNA deletion, amplification, insertion and other types of variation evaluated by next generation sequence(NGS).
Description
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.
Time Frame
2 months
Title
Proportions of lymphocytes, stromal cells, tumor cells in tumor tissue assessed by single cell transcriptome sequence.
Description
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.
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
Title
Incidence rate of gene deletion, amplification, insertion and other types of variation of tumor evaluated by whole exon sequence(WES).
Description
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.
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
Title
Tumor associated proteins expression level of tumor
Description
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.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhang Xiaotian, MD
Phone
13810995536
Email
zhangxiaotianmed@163.com
Facility Information:
Facility Name
Beijing Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shen Lin, Professor
Phone
010-88196561
Email
Linshenpku@163.com
First Name & Middle Initial & Last Name & Degree
Shen Lin, professor

12. IPD Sharing Statement

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

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