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NCT Number: NCT06725342

HNSCC Immuno-genomics Project

For locally advanced and recurrent / metastatic head & neck squamous cell carcinoma (HNSCC), the is an unmet need for the development of efficient treatment combinations, particularly with immune checkpoint inhibitors. HNSCC have been characterized at the genetic / molecular level concerning characteristics of malignancy and potential clinical actionability ; currently, however, the integration of molecular characteristics of both the malignant cells and the host immune response are considered fundamental for the selection of treatment that best suits these patients .

The primary objective of the NCR-17-12885 project is to classify HNSCC for the selection of optimal therapeutic interventions for the patients, based on genomic characteristics and mutational processes operating in these tumours and on the prevailing activated immune pathways.

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Key information

Conditions

Molecular Classification of HNSCC Head and Neck Neoplasms Neoplasms Neoplasms by Site

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Observational

About this study

Herein we propose the development of a combined genomic and gene expression assay for the comprehensive evaluation of HNSCC for the classification of tumors into (a) those with activated checkpoint molecules and activated T cells, likely to respond to checkpoint inhibition in the case of non-operable disease or recurrent disease without prior treatment; (b) those with inducible checkpoint and T cell response prior to the administration of checkpoint inhibitors; (c) those with activated early inflammatory response that needs to be transformed to cell mediated activation; and (d) those with stable genomes and no immune activation probably necessitating induction of genomic instability and T cell activation.

The test to be developed will provide information on the genomic integrity of the tumor and on a global immune related gene expression profile, both by next generation sequencing

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

-Patients with locally advanced squamous cell carcinoma of the head and neck who were treated with concurrent chemoradiotherapy (CCRT) with or without induction chemotherapy (IC) or radical surgery +/- radiotherapy for laryngeal tumors.

Exclusion criteria

  • Age <18 years old
  • Non-squamous cell carcinomas of the head and neck.

Treatment and study plan

Combined DNA/RNA sequencing on clinical FFPE material (technically challenging; innovative); immuno-genomics test.

Genetic

Dual extractions (DNA/RNA) will be carried out from macrodissected thick unstained FFPE sections; samples will be measured for adequate quality / quantity; libraries will be constructed separately with each panel and samples will be sequenced in the same chip in an Ion Torrent Proton System, according to the manufacturer's instructions.

Sequencing results will be called with the Variant Caller for each panel and submitted for initial analysis and annotation to the Ion Reporter pipeline with each DNA and RNA panel

Primary outcomes

  1. Classification of HNSCC based on their genomic and immune-related gene expression characteristics.

    Time frame: 5 years

    To classify HNSCC for the selection of optimal therapeutic interventions for the patients; classification will be based on present genomic characteristics and mutational processes behind them, and on the prevailing activated immune pathways.

Secondary outcomes

  1. Report on analytical performance of the test

    Time frame: 5 years

    (orthogonal validation with dd-sequencing for genomic variants and comparison of RNA sequencing profiles with the existing Illumina DASL gene expression profiling data

  2. HNSCC classification for comparison with (a) PD-L1 IHC (SP263 assay), and (b) the combined IFNG/PD-L1 mRNA ratio (qRT-PCR)

    Time frame: 5 years

    PD-L1 will be tested by immunohistochemistry and IFNG/PD-L1 mRNA ratio by qRT-PCR

  3. Provision of genomic markers predicting for immune status classes

    Time frame: 10 years

    Provision of genomic markers (DNA) predicting for immune status classes (RNA) and vice versa in HNSCC

  4. One step "immuno-genomics test"

    Time frame: 10 years

    Identification of associations between genomic characteristics and immune response-related gene expression, as well as deaminase or other innate mutagen gene expression. Utillization of existing bioinformatics tools. Predictions will be validated for IFNG and PD-L1 expression, different groups of cell mediated cytotoxicity, early and late inflammatory response gene expression, APOBEC and DNA repair gene expression. The aim is to finally produce a simple genomic test (because knowing the genomic status is currently unavoidable) reliably reflecting the status and potential dynamics of the tumor-host microenvironment.

  5. Reclassification of HNSCC with the "immuno-genomics test"

    Time frame: 10 years

    Molecular classification of HNSCC based on immuno-genomics test

  6. Publication of the results

    Time frame: 10 years

    Publication of results for further expolitation

Sponsors and collaborators

Lead sponsor

Hellenic Cooperative Oncology Group

Other

Registry information

Official study title

Immune Response Dynamics Predicted by Genomic Patterns in Head and Neck Cancer (HNSCC): a Translational Research Study of the Hellenic Cooperative Oncology Group

Important dates

Study start
2014
Primary completion
2019
Study completion
2024
First posted
Dec 10, 2024
Registry last updated
Dec 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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