Analysis of Tumor Mutations and Tumor Microenvironment Using Archival Paraffin-embedded Tumor Specimens

Genomic alterations have long been recognized as an important factor in tumor formation and drive tumor cell growth. However, the degree of genomic mutation (tumor mutation load, TMB) varies widely between tumors. In addition to gene mutations in tumor cells, the extent of immune cell infiltration in tumor tissues and the type and nature of immune cells (tumor microenvironment, TME) also play an important role in controlling tumor growth.

In recent years, more and more clinical studies have shown that the degree of genomic alteration (TMB) and tumor microenvironment (TME) have great potential in predicting a cancer patients' response to immunotherapy. Therefore, understanding the interaction and correlation between genomic alteration and tumor immune environment will not only deepen our understanding of tumor biology but also provide an important reference for developing immunotherapy treatment strategies for solid tumors.

Study Overview

• Status: Unknown
• Conditions: Sequence Analysis
• Intervention / Treatment: Other: non intervention

Detailed Description

This is a non-interventional, mono-centric retrospective study to be carried out in Chi Mei Medical Center (CMMC) in order to determine the association between the genomic alterations and gene expression level of immune-related genes in cancer. Samples in paraffin-embedded block of biopsies or surgical pieces (either primary tumor or metastases) will be analyzed. For each sample, clinically relevant data associated with treated cancer and needed for characterization of tumor microenvironment will be documented. No additional procedures besides those already used in the routine clinical practice will be applied to the patients. Treatment assignment will be done according to the current practice.

This trial is, through accessing to archival tumor materials, to establish the relationship between tumor mutation burden and tumor immune microenvironment for future immunotherapy strategy.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: ACT Genomics ACT Genomics; Phone Number: +886-2-2795-3660; Email: peifangchung@actgenomics.com
• Study Contact Backup: Name: Pei-Fang Chung; Phone Number: 1303 +886-2-2795-3660

Study Locations

• Taiwan
  • Taipei, Taiwan, 114
    • Recruiting
    • ACT Genomics
    • Contact: Chung; Phone Number: 1303 886-2-27953660; Email: peifangchung@actgenomics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

600 cancer patients who fulfill the eligibiltiy criteria will be selected from the CMMC tissue bank. Eligible patients should have an available archival paraffin-embedded tumor block stored at the Department of Pathology, CMMC.

Description

Inclusion Criteria:

• Sample from patients with histologically documented cancer in target population.

Exclusion Criteria:

• Unusable sample or biologically deteriorated.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between TMB and the expression level of PD-1/PD-L1	To explore possible relationship between genomic alteration and expression of immune-related genes in solid tumor, tumor mutation burden (TMB) and PD-1/PD-L1 expression level are examined and such relationship will be calculated by Pearson's correlation coefficient.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single point mutations, as part of cancer genomic profile	To establish a cancer genomic profile for the Asian population, genomic alterations such as point mutations will be assessed by NGS-based ACTOnco assay.	12 months
Small insertions and deletions (Indel), as part of cancer genomic profile	To establish a cancer genomic profile for the Asian population, genomic alterations such as small insertions and deletions will be assessed by NGS-based ACTOnco assay.	12 months
Copy number alterations, as part of cancer genomic profile	To establish a cancer genomic profile for the Asian population, genomic alterations such as copy number alterations will be assessed by NGS-based ACTOnco assay.	12 months
Microsatellite instability, as part of genomic profile	To establish a cancer genomic profile for the Asian population, genomic alterations such as microsatellite instability will be assessed by NGS-based ACTOnco assay.	12 months
TME gene expression profile, which consists of quantitative measurements of immune-related genes	To establish an expression signature of tumor microenvironment (TME) in addition to PD-1 and PD-L1, >90 immune-related genes will be assessed by ACTTME assay via quantitative PCR	12 months
Concordance of TMB between ACTOnco assay and an externally validated assay	To compare between calculated tumor mutation burden values (TMB, in mutations per megabase) resulting from different methodologies, concordance between two NGS-based assays will be expressed as positive predictive value (PPV) and negative predictive value (NPV).	12 months

Collaborators and Investigators

• Sponsor: ACT Genomics
• Collaborators: Chi Mei Medical Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (Actual): October 25, 2018

Study Record Updates

• Last Update Posted (Actual): October 29, 2018
• Last Update Submitted That Met QC Criteria: October 26, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Genomic profiling assay
• Other Study ID Numbers: ACTG-18001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No