HNSCC Immuno-genomics Project

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

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.

Study Overview

• Status: Completed
• Conditions: Molecular Classification of HNSCC
• Intervention / Treatment: Genetic: Combined DNA/RNA sequencing on clinical FFPE material (technically challenging; innovative); immuno-genomics test.

Detailed Description

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

• Study Type: Observational
• Enrollment (Actual): 401

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Classification of HNSCC based on their genomic and immune-related gene expression characteristics.	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.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Report on analytical performance of the test	(orthogonal validation with dd-sequencing for genomic variants and comparison of RNA sequencing profiles with the existing Illumina DASL gene expression profiling data	5 years
HNSCC classification for comparison with (a) PD-L1 IHC (SP263 assay), and (b) the combined IFNG/PD-L1 mRNA ratio (qRT-PCR)	PD-L1 will be tested by immunohistochemistry and IFNG/PD-L1 mRNA ratio by qRT-PCR	5 years
Provision of genomic markers predicting for immune status classes	Provision of genomic markers (DNA) predicting for immune status classes (RNA) and vice versa in HNSCC	10 years
One step "immuno-genomics test"	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.	10 years
Reclassification of HNSCC with the "immuno-genomics test"	Molecular classification of HNSCC based on immuno-genomics test	10 years
Publication of the results	Publication of results for further expolitation	10 years

Collaborators and Investigators

• Sponsor: Hellenic Cooperative Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2014
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: December 4, 2024
• First Posted (Estimated): December 10, 2024

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 4, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: genomics; head and neck cancer; immune-related gene expression
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: ΗΕ5R/18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No