Clinical trial NCT05375266: Immune Biomarker Study for Head and Neck Cancer
Official title: Immune Biomarker Study for Head and Neck Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Head and Neck Cancer
Oral Cavity Cancer
Oropharyngeal Cancer
Hypopharyngeal Cancer
Laryngeal Cancer
Keywords: Immunologic markers
Immunotherapy
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
Collaborators: name: University Hospital Erlangen
name: University Hospital Regensburg
name: University Hospital Augsburg
First posted: 2022-05-16
Enrollment: 1100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting for treatment at the participating study centers and meeting the inclusion criteria

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 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
Secondary outcomes:
measure: Longitudinal immunophenotyping of the patients: Detection of about 30 distinct immune cell (sub)types together with their activation markers during study period
timeFrame: 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
measure: Analysis of cytokines in peripheral blood and their change at certain points in the course of treatment
timeFrame: 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
measure: Determination of transcription processes in the immune cells at certain points in the course of treatment to extend the prognostic immune signature
timeFrame: 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
measure: Analysis of patient's metabolic state
timeFrame: 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
measure: Analysis of patient's microbiomic state by examination of saliva, tumor and stool
timeFrame: The analyses are conducted at time point before surgery (day 0)
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: ENT - Head and Neck Surgery Department
state: Bavaria
city: Erlangen
country: Germany
facility: Maxillo-Facial-Surgery Department
state: Bavaria
city: Erlangen
country: Germany
facility: Radiation Oncology Department
state: Bavaria
Study officials:
affiliation: ENT - Head and Neck Surgery Department, University of Erlangen-Nurnberg
name: Antoniu-Oreste Gostian, PD Dr. med.
role: STUDY_DIRECTOR
affiliation: Radiation Oncology, University of Erlangen-Nurnberg
name: Markus Hecht, PD Dr. med.
role: STUDY_DIRECTOR
affiliation: Maxillo-facial-surgery, University of Erlangen-Nurnberg
name: Manuel Weber, PD Dr. med. Dr. med. dent.
role: PRINCIPAL_INVESTIGATOR
affiliation: Translational Radiobiology, University of Erlangen-Nurnberg
name: Udo Gaipl, Prof. Dr. rer. nat. habil.
role: PRINCIPAL_INVESTIGATOR
affiliation: Translational Radiobiology, University of Erlangen-Nurnberg
name: Benjamin Frey, PD Dr.-Ing. Dr. habil. med.
role: PRINCIPAL_INVESTIGATOR
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