Characterisation of TLR4+ Blood Cells in Patients With Solid Cancer

NCT ID: NCT06131775

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-29
• Study Completion Date: 2028-05-01

Brief Summary

The potential of immunotherapy in the treatment of cancer is now well documented. While excessive activation of the immune system may be associated with severe reactions and/or auto-immune syndromes, it is now clearly established that controlled activation of the adaptive immune system constitutes a major contribution to the treatment of cancer. Antigen-independent activation of the adaptative immune system with " immune checkpoint inhibitors " (ICI) has allowed prolonged survival in a minority of patients with previously intractable disease. However, a variety of tumor indications are still presently inaccessible to immunotherapeutic approaches or poorly responsive to these therapies.

The immune system is a highly reactive complex comprising antigen-specific cells (adaptive immune system) and antigen-agnostic cells (innate immune system) which interact closely in a complex network. The adaptive immune response is mediated by B and T cells upon antigen-specific recognition. The innate response is mediated by macrophages, dendritic cells, Natural Killer cells and assume the immediate defense of the organism against infectious agents. The innate immune system plays a key role in antigen processing and presentation, production of key cytokines and as anti-tumor effector cells. The role of the innate immune system in the control of cancer progression and in cancer therapy is well documented. Natural Killer cells, involved in antibody-dependent cellular cytotoxicity, and cells performing phagocytosis such as macrophages and neutrophils, participate in tumor destruction after intervention of adaptive immune cells and in combination with certain tumor-targeting therapies, such as antibodies recognizing tumor-specific antigens.

The Odyssey project aims to harness the next generation paradigm of cancer immunotherapy : systemic stimulation of the innate immune system.

To achieve this endeavour the investigator will exploit a well-known yet poorly documented phenomenon, i.e. the rare occurrence of cure in cancer patients who have presented a simultaneous severe septic episode at the time of diagnosis.

Several clinical studies have been realized in order to demonstrate the effect of the innate immune response activation by the bacterial LPS (lipopolysaccharides) in cancer therapy. However, severe toxicities have been described even at very low dose of LPS. The LPS-activated immune response is mediated by TLR4 (Toll Like Receptor 4), a transmembrane receptor expressed by several cell types including monocytes and macrophages. The interaction of TLR4 with LPS mainly induces the release of proinflammatory cytokines (so called " canonical pathway "). TLR4-signalling cascade can also induce the release of type I interferon (so called " alternative pathway "), a class of cytokines known to promote antitumoral activity. LPS tolerance is presumed to be rather associated with the activation of the alternative pathway. Therefore, managing this LPS tolerance is a key mechanism that could limit the systemic toxicity of LPS while stimulating the innate immune system.

Héphaïstos-Pharma biotech and the CRCL Onco-Pharmacology lab (Centre de Recherche en Cancérologie de Lyon) have set up a modified formulation of the LPS that improves its pharmacokinetic properties, reduces its toxicity, and preferentially activates TLR4-alternative signalling pathway. Before investigating the effect of this new immunostimulant in a future phase I/II clinical trial, a translational study is required to further characterize the TLR4 positive cells population as well as the innate immune system in patients with solid cancer.

Conditions

All Types of Solid Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Immunotherapy

Patients with locally advanced/metastatic disease who are due to receive as a first attempt an immune checkpoint inhibitors immunotherapy-based treatment.

Blood sample collection : One blood draw of 10 mL will be realized before the initiation of immunotherapy. Any adverse event related to the blood draw will be recorded. A follow-up will be performed at 6 months to record the immune-related adverse events, a statement of the disease and any other cancer treatments received. A 24 months long term follow up will be performed to record patient vital status and any date of disease progression.

Group Type: OTHER

Blood sampling

Intervention Type: BIOLOGICAL

One blood sample of 10mL is realized before initiation of immunotherapy

Curative surgery

Patients newly diagnosed and naive of any anticancer treatment who are due to receive a curative surgery of their primitive tumor.

Blood samples collection : Three blood draws of 10 mL will be realized : one before the surgery, one after 3 months and one after 6 months. Any adverse event related to the blood draw will be recorded. A follow-up will be performed at 6 months to record the statement of the disease and any other cancer treatments received. A 24 months long term follow up will be performed to record patient vital status and any date of disease relapse.

Group Type: OTHER

Blood sampling

Intervention Type: BIOLOGICAL

Three blood samples of 10mL are realized at distinct steps of patients disease management : one before the curative surgery, one after three months and one after six months.

Interventions

Blood sampling

One blood sample of 10mL is realized before initiation of immunotherapy

Intervention Type: BIOLOGICAL

Blood sampling

Three blood samples of 10mL are realized at distinct steps of patients disease management : one before the curative surgery, one after three months and one after six months.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patient older than 18 years
• Patient who gave its written informed consent to participate to the study
• Patient with histologically confirmed diagnosis of any type of malignancy (solid tumors)
• Patient with a minimum of 6 months life expectation at inclusion
• Patient covered by a medical insurance

• Patient with metastatic disease or unresectable locally advanced malignancy (solid tumors) who is naive of immune checkpoint inhibitors (ICI)-based immunotherapy and is due to initiate an ICI immunotherapy alone or in combination with any other systemic anticancer treatment.

• Patient with a diagnosed malignancy amenable to surgery with curative intent who is naive of any anticancer treatment

Exclusion Criteria

• Patient with secondary malignancy unless this malignancy is cured with no evidence of recurrence for at least 5 years.
• Pregnant or breastfeeding woman or expecting to conceive
• Patient who is deprived of liberty due to judicial or administrative decision
• Patient with known psychiatric disorders that would interfere with cooperation with the requirements of the trial
• Patient admitted in a social or sanitary institution for an objective other than the one of this trial
• Adult patient under legal protection

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

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pneumology Unit

Bron, , France

Site Status: RECRUITING

Dermatology Unit

Pierre-Bénite, , France

Site Status: RECRUITING

Oncological and Gynecological Surgery Unit,

Pierre-Bénite, , France

Site Status: RECRUITING

Oncology Unit, Hospices Civils de Lyon Sud

Pierre-Bénite, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Charles DUMONTET, MD

Role: CONTACT

charles.dumontet@chu-lyon.fr

06 82 13 66 14 ext. 33

Angelique STUANI

Role: CONTACT

angelique.stuani@chu-lyon.fr

04 78 86 23 76 ext. 33

Facility Contacts

Michael DURUISSEAUX, MD

Role: primary

michael.duruisseaux@chu-lyon.fr

04 72 35 76 44 ext. 33

Stephane DALLE, MD

Role: primary

stephane.dalle@chu-lyon.fr

04 78 86 16 28 ext. 33

François GOLFIER, MD

Role: primary

francois.golfier@chu-lyon.fr

04 78 86 41 78 ext. 33

Benoit YOU, MD

Role: primary

Benoit.you@chu-lyon.fr

04 78 86 43 53 ext. 33

Other Identifiers

2023-A01542-43

Identifier Type: OTHER

Identifier Source: secondary_id

69HCL23_0596

Identifier Type: -

Identifier Source: org_study_id