Identification of Individual Histological and Blood Markers in Patients With Recurrent or Metastatic Upper Aerodigestive Tract Squamous Cell Carcinoma in Response to Immunotherapies (iMonitORL)

November 27, 2023 updated by: Fondation Hôpital Saint-Joseph

Epidermoid Carcinoma of the Upper Aerodigestive Tract (CEVADS) is the 6th most common cancer worldwide. Despite current therapies (radiotherapy, surgery and chemotherapy), cancers of the Upper Aerodigestive Tract (UAT) have a poor prognosis, with a 10-year survival rate of no more than 20%.

For recurrent or metastatic CEVADS, the therapeutic arsenal, based for many years on chemotherapy and anti-EGFR (Epidermal Growth Factor Receptor) agents, has been enriched by a new therapeutic class: PD-1 inhibitors. For CEVADS, PD-1 inhibitors have been approved for second-line treatment of nivolumab for over a year, and are now used in first-line treatment of pembrolizumab.

The results of this therapeutic class in CEVADS are not as spectacular as for melanoma or bronchial cancer. Indeed, only 20% of patients have a favorable response, compared with half who experience disease progression. This low proportion of responders can be explained by tumor heterogeneity within CEVADS and poor patient selection.

The only marker used to select patients is PD-L1 expression detected by ImmunoHistochemistry (IHC). However, it seems that this marker, described as imperfect, is still little explored in ENT. It needs to be compared with the expression of other cell lines in the tumor microenvironment, which could play an important role in resistance to PD-1 inhibitors.

IHC identifies all macrophages using the CD68 marker, while the CD163 marker is specific to M2 macrophages.

Other targets in the microenvironment are also being investigated, with the discovery of a Tertiary Lymphocyte Structure (TLS) in melanoma treated with immunotherapy.

It therefore seems necessary to gain a better understanding of the mechanisms of tumor progression under immunotherapy in order to develop strategies to optimize response to treatment. This would enable better selection of patients likely to benefit from immunotherapy, and open up prospects for therapeutic combinations.

The hypothesis is that macrophages, but also other cells and factors in the CEVADS microenvironment, play a decisive role in resistance to PD-1 inhibitors. The aim is therefore to continue these macrophage analyses, extend them to other cells in the microenvironment and link them to other prognostic factors under investigation.

A prospective study will analyze tumor tissue during treatment with PD-1 inhibitors, in order to correlate all the factors studied with response or resistance to immunotherapies.

In addition, the oral microbiota, in the lineage of the intestinal microbiota, has been shown to be highly stable over time and to play a role in the oncogenesis of certain cancers, notably CEVADS. Like the intestinal microbiota, it could also represent a prognostic factor in the response to immunotherapies.

Of all the bacteria in this oral microbiota, one has been shown to play a major role: Fusobacterium nucleatum (F. nucleatum). However, little is known about the mechanism of action of intratumoral F. nucleatum on the development of CEVADS. In particular, it is thought to play a role in local cancer immunity, via macrophages, regulatory T cells (Tregs) and TLRs. Finally, it appears that specific antimicrobial T-cell responses may cross-react with tumor antigens, hence the importance of also analyzing the metabolome of commensal bacteria.The aim of this study was to evaluate the evolution of the presence of this bacterium in saliva, as well as the specific immune response to F. nucleatum in patients with CEVADS during immunotherapy treatment.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Helene BEAUSSIER, PharmD, PhD

Study Locations

  • France
      • Paris, France
        • Hôpital Bichat
        • Contact:
          • Diane EVRARD, MD
      • Paris, France
        • Hôpital Saint-Louis
        • Contact:
          • Sandrine FAIVRE, MD, PhD
      • Paris, France, 75014
        • Hôpital Saint-Joseph
        • Contact:
          • Eric RAYMOND, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients aged ≥ 18 years
  • Patients with histologically confirmed CEVADS involving the oral cavity, oropharynx, hypopharynx or larynx
  • Pre-treated patients with a first recurrence (locoregional or metastatic) who are candidates for immunotherapy
  • Patient affiliated to a health insurance plan
  • French-speaking patient
  • Patient with free, informed and written consent

Exclusion Criteria:

  • Patients with a contraindication to immunotherapy (transplant patients)
  • Pregnant or breast-feeding patients
  • Patient under guardianship or curatorship
  • Patient under court protection
  • Patient deprived of liberty

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: procedure/surgery: Tumor biopsy
Following the start of immunotherapy, an ENT surgeon will perform a cervico-facial tumor biopsy between D30 and D180.
Procedure: Tumor Biopsy

Following the start of immunotherapy, an ENT surgeon will perform a cervico-facial tumor biopsy between D30 and D180. This will only be carried out if the tumour tissue is externalized and therefore accessible, and if the biopsy can be performed under local anaesthetic without any constraints for the patient (pain, risk of bleeding).

It consists of a superficial sampling of the externalized tumour lesion under local anaesthetic (xylocaine spray 5%, or xylocaine injectable 1%).

Biopsy of cervico-facial lesions under local anaesthetic is a commonly performed procedure. The main risk of this procedure is bleeding, which is very rare.

The biopsy will not be performed if the surgeon considers that the risk of bleeding is too great. Given the externalized nature of the lesion, biopsy does not entail any risk of tumour dissemination (possible for deep biopsies).

  • Four 10-mL blood samples from two heparinized tubes
  • Four 5-mL unstimulated saliva samples: non-invasive examination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histological markers linked to the clinical benefit of immunotherapies
Time Frame: Month 6
This outcome corresponds to the number of patients presenting a clinical benefit: objective response or stable disease according to RECIST v1.1 dimensional criteria, and the number of patients presenting tumor progression as the best response to immunotherapy.
Month 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histological markers linked to survival
Time Frame: Month 6
This outcome corresponds to the time elapsed between initiation of immunotherapy and death, all causes combined.
Month 6
Expression of histological markers with PD-L1 expression
Time Frame: Month 6
This outcome corresponds to the quantitative or semi-quantitative evolution of each marker including incidence of macrophages, lymphocytes, epithelial-mesenchymal transition markers) and blood (including Squamous Cell Carcinoma (SCC), neutrophil/lymphocyte ratio, circulating macrophages and lymphocytes), compared with the quantitative evolution of PD-L1 expression.
Month 6
Presence of Fusobacterium nucleatum in the oral microbiota
Time Frame: Month 6
This outcome corresponds to the presence of Fusobacterium nucleatum in the oral microbiota by microbial DNA detection.
Month 6
Presence of an IgG or IgA anti-Fusobacterium nucleatum humoral response
Time Frame: Month 6
This outcome corresponds to the presence of an anti-F. nuc IgG or IgA humoral response in patients' serum before and after immunotherapy treatment.
Month 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondation Hôpital Saint-Joseph

Investigators

  • Study Director: Eric Raymond, MD, PhD, Hopital Paris Saint-Joseph

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 30, 2023

Primary Completion (Estimated)

December 29, 2025

Study Completion (Estimated)

June 30, 2026

Study Registration Dates

First Submitted

September 11, 2023

First Submitted That Met QC Criteria

September 25, 2023

First Posted (Actual)

September 29, 2023

Study Record Updates

Last Update Posted (Actual)

November 28, 2023

Last Update Submitted That Met QC Criteria

November 27, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • iMonitORL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Squamous Cell Carcinoma of the Oropharynx

Clinical Trials on Tumor Biopsy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Madagascar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe