ImmunBio-KHT: Immune Biomarker Study for Head and Neck Cancer

Sponsor

University of Erlangen-Nürnberg Medical School (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05375266

Collaborator

University Hospital Erlangen (Other), University Hospital Regensburg (Other), University Hospital Augsburg (Other)

1,100

Enrollment

58.5

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The aim of this prospective non-interventional multi-center trial is to study the prognostic value of intratumoral and systemic immune biomarkers in newly diagnosed non-metastatic head and neck cancer. Furthermore, the local immunological processes in the tumor will be correlated with the systemic immune status determined in the peripheral blood to identify prognostic immune signatures. In addition, tumor organoids will be generated ex vivo for functional biological analyses. The main objective is to create a prognostic score determined by clusters based on tumor immunologic criteria.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer Oral Cavity Cancer Oropharyngeal Cancer Hypopharyngeal Cancer Laryngeal Cancer	Other: Sampling

Detailed Description

Except for human papillomavirus(HPV)-associated oropharyngeal cancer, immunological biomarkers do not influence treatment algorithms in locally advanced head and neck cancer. In the meantime, a prognostic significance of tumor infiltrating lymphocytes has been recognized. However, these biomarkers do not influence clinical decisions. This may be due to previous focus on the entire group of heterogeneous squamous cell carcinomas in the head and neck region, while the tumor localization has been neglected. In addition, the isolated observation of singular immune cell populations may not be sufficient with regard to the complex interactions of the tumor with the local and systemic immune system, e.g. the presence of regulatory T cells (FoxP3+) in immunologically highly active tumors ("inflamed" or "hot") improves the prognosis, whereas the prognosis is worsened in immunologically less active tumors ("immune desert").The immune checkpoint molecule programmed death-ligand 1 (PD-L1) is currently used as a single predictive marker for immunotherapy with PD(L)-1 inhibitors. Certainly, combined prospective analyses of immune cells and immune checkpoint molecules in large patient cohorts are scarce so far. Of note, the prognostic relevance of immune cells and immunologically active substances in the peripheral blood serving as makers for immunotherapies has already been described. Yet prognostic and predictive markers in the peripheral blood have rarely been studied or linked to the local tumor immune status. However, analyses of single biomarkers of local and systemic immune responses and different immune cell populations can be expected to gain prognostic precision through cluster formation and allow grouping of head and neck tumors according to immunobiological criteria rather than anatomic localization. Therefore, the investigators expect to be able to identify an immunobiological biomarker signature for head and neck tumors that will contribute to the development of future individualized treatment approaches leading to precision head and neck oncology.

Study Design

Study Type:

Observational

Anticipated Enrollment :

1100 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Immune Biomarker Study for Head and Neck Cancer

Anticipated Study Start Date :

May 16, 2022

Anticipated Primary Completion Date :

Mar 31, 2026

Anticipated Study Completion Date :

Mar 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Study Cohort The study cohort consist of patients with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, paranasal sinuses or larynx in stage UICC (Union internationale contre le cancer) II-IVB	Other: Sampling This is an observational study. Consequently, study participation does not alter the therapy of the treated disease. Blood will be drawn from patients at several time points during and after radiotherapy (RT) and therapy with immune checkpoint inhibitor (ICI) for detailed immunomonitoring of the patients. In addition, faeces and sputum of the patients for microbiomic and metabolomic measures will be collected. Whenever possible, adequate tissue samples are taken from the center of the tumor and a biopsy is taken from the edge of the tumor including the adjacent mucosa in the nearby area without affecting the pathological assessment (study group). Blood, faeces and sputum will be taken from patients of the control group prior to surgery. After surgery, only blood will be taken.
Control Group The control group consists of patients with no current diagnoses of cancer undergoing surgery at the participating medical center	Other: Sampling This is an observational study. Consequently, study participation does not alter the therapy of the treated disease. Blood will be drawn from patients at several time points during and after radiotherapy (RT) and therapy with immune checkpoint inhibitor (ICI) for detailed immunomonitoring of the patients. In addition, faeces and sputum of the patients for microbiomic and metabolomic measures will be collected. Whenever possible, adequate tissue samples are taken from the center of the tumor and a biopsy is taken from the edge of the tumor including the adjacent mucosa in the nearby area without affecting the pathological assessment (study group). Blood, faeces and sputum will be taken from patients of the control group prior to surgery. After surgery, only blood will be taken.

Arm

Intervention/Treatment

Study Cohort

The study cohort consist of patients with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, paranasal sinuses or larynx in stage UICC (Union internationale contre le cancer) II-IVB

Other: Sampling

This is an observational study. Consequently, study participation does not alter the therapy of the treated disease. Blood will be drawn from patients at several time points during and after radiotherapy (RT) and therapy with immune checkpoint inhibitor (ICI) for detailed immunomonitoring of the patients. In addition, faeces and sputum of the patients for microbiomic and metabolomic measures will be collected. Whenever possible, adequate tissue samples are taken from the center of the tumor and a biopsy is taken from the edge of the tumor including the adjacent mucosa in the nearby area without affecting the pathological assessment (study group). Blood, faeces and sputum will be taken from patients of the control group prior to surgery. After surgery, only blood will be taken.

Control Group

The control group consists of patients with no current diagnoses of cancer undergoing surgery at the participating medical center

Other: Sampling

Outcome Measures

Primary Outcome Measures

Observation of changes in an established immune matrix (intratumoral and systemic) of responding/non-responding patients at certain points in time in the course of treatment [Change of the immune matrix from baseline (before surgery; day0) and after surgery (day 7) and at the end of radiotherapy (day 60-70) and end of study period up to 5 years]
Based on the intrinsic immunological biology of the tumors, different immune cells and tumor cell markers will characterize immunological groups using cluster analysis. Immune matrix of patients assessed by LIPS (liquid immune profile-based signature) (acc. Zhou et al. JITC 2021) and Tumour Associated Lymphocytes (TAL).

Secondary Outcome Measures

Longitudinal immunophenotyping of the patients: Detection of about 30 distinct immune cell (sub)types together with their activation markers during study period [The analyses are conducted at time points before (day 0) surgery and after surgery (day 7) as well as at the end of radiotherapy (day 70-80) or end of study period up to 5 years]
The distribution of immune cells and messenger substances in the blood will be examined by means of immunophenotyping in order to add the systemic immune cell composition. Flow cytometric assessment of the amount of circulating immune cell-distribution per milliliter whole blood according to the LIPS (liquid immune profile-based signature) technique (Zhou et al. JITC 2021).
Analysis of cytokines in peripheral blood and their change at certain points in the course of treatment [The analyses are conducted at time points before (day 0) surgery and after surgery (day 7) as well as at the end of radiotherapy (day 70-80) or end of study period up to 5 years]
Electrochemiluminescent MULTI-ARRAY measurement of concentration (pg/ml whole blood) cytokines/chemoattractant cytokines in the serum/plasma of the patients according to the LIPS (liquid immune profile-based signature) technique (Zhou et al. JITC 2021).
Determination of transcription processes in the immune cells at certain points in the course of treatment to extend the prognostic immune signature [The analyses are conducted at time points before (day 0) surgery and after Surgery (day 7) as well as at the end of radiotherapy (day 70-80) or end of study period up to 5 years]
Genetic profiling (Whole exome sequencing, RNASeq, ddPCR, realtimePCR) of transcribed genes in blood lymphocytes.
Analysis of patient's metabolic state [The analyses are conducted at time points before (day 0) surgery and after Surgery (day 7) as well as at the end of radiotherapy (day 70-80) or end of study period up to 5 years]
Massspectometric untargeted metabolomic of patients serum/plasma to assess the change of metabolites (pg/ml whole blood) from baseline to end of radiotherapy.
Analysis of patient's microbiomic state by examination of saliva, tumor and stool [The analyses are conducted at time point before surgery (day 0)]
16S rRNA deep sequencing of microbiome in salvia, tumour and stool samples to assess the presence and relative distribution of microbiotes (Operational taxonomic units [OTUs]).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Initial diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, paranasal sinuses or larynx in stage UICC II-IVB (study group)
Diseases other than malignant diseases (patients with the indication for surgery of the ear, nose nose or maxillofacial surgery) (control group)
Absence of a currently existing or previous malignant disease regardless of the anatomical localization (control group)
Agreement of the patients for sampling blood, saliva and stool as well as consent to the preservation of all samples for further study purposes
Age ≥ 18 years
Cognitive ability of the patients to understand the meaning and purpose of the study and agree to it

Exclusion Criteria:

Distant metastases and / or simultaneous secondary carcinoma at the time of diagnosis (= inclusion date)
Carcinomas in which it is (likely) impossible to take a sample without interfering with the further pathological assessment
Present drug abuse
Patients who are unable or unwilling to behave and receive treatment according to protocol
Patients who are legally patronized
Patients who are not eligible for participation in the study due to language barrier

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Erlangen-Nürnberg Medical School
University Hospital Erlangen
University Hospital Regensburg
University Hospital Augsburg

Investigators

Study Director: Antoniu-Oreste Gostian, PD Dr. med., ENT - Head and Neck Surgery Department, University of Erlangen-Nurnberg
Study Director: Markus Hecht, PD Dr. med., Radiation Oncology, University of Erlangen-Nurnberg
Principal Investigator: Manuel Weber, PD Dr. med. Dr. med. dent., Maxillo-facial-surgery, University of Erlangen-Nurnberg
Principal Investigator: Udo Gaipl, Prof. Dr. rer. nat. habil., Translational Radiobiology, University of Erlangen-Nurnberg
Principal Investigator: Benjamin Frey, PD Dr.-Ing. Dr. habil. med., Translational Radiobiology, University of Erlangen-Nurnberg