All Types of Solid CancerODYSSEENCT06131775
Characterisation of TLR4+ Blood Cells in Patients With Solid Cancer
A study testing Blood sampling in people with All Types of Solid Cancer, run by Hospices Civils de Lyon at 4 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- All Types of Solid Cancer
- What is being tested?
- Blood sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 4 sitesFrance
- Study dates
- 29 May 2024to 1 May 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France4 sites, 4 recruiting
- Recruiting
Pneumology Unit
Bron, 69500
Michael DURUISSEAUX, MD, 04 72 35 76 44 ext. 33, michael.duruisseaux@chu-lyon.fr
- Recruiting
Dermatology Unit
Pierre-Bénite, 69495
Stephane DALLE, MD, 04 78 86 16 28 ext. 33, stephane.dalle@chu-lyon.fr
- Recruiting
Oncological and Gynecological Surgery Unit,
Pierre-Bénite, 69495
François GOLFIER, MD, 04 78 86 41 78 ext. 33, francois.golfier@chu-lyon.fr
- Recruiting
Oncology Unit, Hospices Civils de Lyon Sud
Pierre-Bénite, 69495
Benoit YOU, MD, 04 78 86 43 53 ext. 33, Benoit.you@chu-lyon.fr
About this study
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.
Read more
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
- Being tested
- Blood sampling
- Keywords
- Immunotherapy, Innate immune system systemic activation, TLR4 positive immune cells, Lipopolysaccharides, Immunostimulant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingBiological
One blood sample of 10mL is realized before initiation of immunotherapy
Blood samplingBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy | Other | 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. Receives: Biological: Blood sampling |
| Curative surgery | Other | 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. Receives: Biological: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohort 1 : 24 months-progression free survival (24M PFS)
Cohort 1 : 24M-PFS defined as the time from the date of the first drug administration to the first documented clinical, biological or radiological progression according to investigator assessment during a period of 24 months. Patients who have not progressed at the time of analysis will be censored at the time of the latest date of assessment.
Measured: 24 months
Cohort 2 : describe the evolution of the percentage of TLR4+ cells in peripheral blood after curative ablation of a cancerous tumour.
Number of TLR4 positive cells before curative surgery and after 3 and 6 months.
Measured: Before surgery, after 3 months and after 6 months.
Secondary outcomes (5)
Overall Survival (OS) Cohorts 1 and 2
OS defined as the time from the date of the day of the treatment to the date of death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
Measured: Baseline,date of death, last recorded date or 24 months
Concentration of innate and adaptive immune cell population Cohorts 1 and 2
Concentration of innate and adaptive immune memory cells in peripheral blood as defined by the expression level of specific immunophenotypic cell surface receptors
Measured: Baseline
LPS-mediated activation of TLR4 positive cells Cohorts 1 and 2
LPS-mediated activation of TLR4 positive cells defined as the expression of the membrane marker CD169
Measured: baseline
Number of high grade (≥3) immune-related adverse events (irAE) Cohort 1
Number of high grade (≥3) irAE(s) 6 months after initiation of immunotherapy
Measured: Baseline ans 6 month
24 months-relapse free survival (24M RFS) Cohort 2
24M-RFS defined as the time from the date of the surgery to the first documented clinical, biological or radiological progression according to investigator assessment during a period of 24 months. Patients who have not relapsed at the time of analysis will be censored at the time of the latest date of assessment.
Measured: Before surgery, after 3 months, after 6 months and after 24 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2023
- Study start29 May 2024
- Primary completion1 May 2028 (estimated)
- Study completion1 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for All Types of Solid CancerStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Cohort
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06131775
- Sponsor's protocol ID
- 69HCL23_0596
- Other IDs
- 2023-A01542-43
- Acronym
- ODYSSEE
- Status last verified
- May 2025
- First submitted
- 13 Oct 2023
- Last updated
- 18 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No