Computational Prediction and Experimental Validation of Gastric Cancer Associated Neoantigens

Gastric Cancer Clinical Trial

Official title:

Computational Prediction and Experimental Validation of Gastric Cancer Associated Neoantigens

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05498194
• Other study ID #: 62/GCN-HDDD
• Status: Not yet recruiting
• Start date: August 15, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2022
• Source: University Medical Center Ho Chi Minh City (UMC)
• Contact: Long Vo Duy
• Phone: +84.918133915
• Email: long.vd[@]umc.edu.vn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is to develop methods for identification of neoantigens from patients with gastric cancer.

Description:

Gastric cancer (GC) is the fourth most common cancer type and one of the leading causes of cancer-related death in Vietnam. Immunotherapy using checkpoint inhibitors (CPI) in combination with certain types of chemotherapy has been clinically shown to offer survival benefits for patients diagnosed with advanced stomach cancer. However, clinical outcomes of CPI are associated with the quantity as well as the quality of neoantigens which arise due to mutations in coding regions of cancer associated genes. Such neoantigens can be presentable by cancer cells to the host adaptive immune system and activate antitumor responses. Hence, the identification of neoantigens would be of significance for immunotherapeutic approaches. Recent data published by the Tumor Neoantigen Selection Alliance (TESLA) indicate that a large proportion (98%) of predicted neoantigens are not immunogenic and ineffective in activating anti-tumor responses. In the present study, we aim to develop a comprehensive pipeline incorporating both computational prediction tools and experimental validation assays to enhance the accuracy of neoantigen identification.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Gender: All
• Age group: 15 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Male or Female patients aged 15 years and older

2. Diagnosed with advanced gastric cancer (T2-4b/N0-3/M0-1 stage, according to the eighth edition of the American Joint Committee on Cancer TNM (AJCC TNM) system)

3. Treatment-Naive

4. Not known for other concomitant cancers

5. Provide written informed consent

Exclusion Criteria:

1. Insufficient tumor tissues (less than 1 cm3)

2. Unable to sign informed consent

3. Underwent treatment

Related Conditions & MeSH terms

• Gastric Cancer
• Neoantigens
• Stomach Neoplasms

Intervention

Diagnostic Test:
• ratio of predicted neoantigens
10 ml of whole blood is collected from each patient prior surgery Fresh tumor tissue samples (~ 1cm3 ) are collected during surgery

Locations

Country	Name	City	State
Vietnam	University Medical Center Ho Chi Minh City	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Ho Chi Minh City (UMC)

Country where clinical trial is conducted

Vietnam, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The neoantigen landscape of patients with gastric cancer	The analysis of tumor DNA and RNA sequencing data will provide the mutational distribution of patients with gastric cancer, which could give rise to neoantigens. Of those, neoantigens derived from hotspot mutations in Vietnamese gastric cancer patients will be identified.	3 months from the beginning of the study
Secondary	The ratio of predicted neoantigens being presented by HLA-I	Computational pipelines will be employed to predict the pairing of neoantigens and HLA molecules. Subsequently, the ratio of those predicted neoantigens will be validated by co-immunoprecipitation with anti-HLA antibodies and mass spectrometry analysis for their binding to corresponding HLA molecules.	6 months from the beginning of the study
Secondary	The ratio of predicted neoantigens being immunogenic.	Immunoassays will be employed to identify neoantigens that could activate CD4 and CD8 T cells to kill tumor cells and serve as putative candidates for immunotherapy.	12 months from the beginning of the study