Immune Biomarker Study for Head and Neck Cancer

NCT ID: NCT05375266

Last Updated: 2023-05-17

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 1100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-16
• Study Completion Date: 2027-03-31

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.

Conditions

Head and Neck Cancer; Oral Cavity Cancer; Oropharyngeal Cancer; Hypopharyngeal Cancer; Laryngeal Cancer

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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

Sampling

Intervention Type: OTHER

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

Sampling

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Erlangen

OTHER

Sponsor Role: collaborator

University Hospital Regensburg

OTHER

Sponsor Role: collaborator

University Hospital Augsburg

OTHER

Sponsor Role: collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antoniu-Oreste Gostian, PD Dr. med.

Role: STUDY_DIRECTOR

ENT - Head and Neck Surgery Department, University of Erlangen-Nurnberg

Markus Hecht, PD Dr. med.

Role: STUDY_DIRECTOR

Radiation Oncology, University of Erlangen-Nurnberg

Manuel Weber, PD Dr. med. Dr. med. dent.

Role: PRINCIPAL_INVESTIGATOR

Maxillo-facial-surgery, University of Erlangen-Nurnberg

Udo Gaipl, Prof. Dr. rer. nat. habil.

Role: PRINCIPAL_INVESTIGATOR

Translational Radiobiology, University of Erlangen-Nurnberg

Benjamin Frey, PD Dr.-Ing. Dr. habil. med.

Role: PRINCIPAL_INVESTIGATOR

Translational Radiobiology, University of Erlangen-Nurnberg

Locations

ENT - Head and Neck Surgery Department

Erlangen, Bavaria, Germany

Site Status: RECRUITING

Maxillo-Facial-Surgery Department

Erlangen, Bavaria, Germany

Site Status: RECRUITING

Radiation Oncology Department

Erlangen, Bavaria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Antoniu-Oreste Gostian, PD Dr. med.

Role: CONTACT

antoniu-oreste.gostian@uk-erlangen.de

+49 9131 85-33156

Facility Contacts

Antoniu-Oreste Gostian, PD Dr. med.

Role: primary

antoniu-oreste.gostian@uk-erlangen.de

+49 9131 85-33156

Manuel Weber, PD Dr. med.

Role: primary

Markus Hecht, PD Dr. med.

Role: primary

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Other Identifiers

12-384-B

Identifier Type: -

Identifier Source: org_study_id