Identification of a Predictive Metabolic Signature of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Carcinoma (METABO-ICI)

January 15, 2024 updated by: University Hospital, Grenoble

: Identification of a Predictive Metabolic Signature of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Carcinoma

Immune checkpoints inhibitors (ICI) are becoming new standards of care for Non-Small Cell Lung Carcinoma (NSCLC) treatment. To date, no powerful predictive biomarker of response has been found.

The investigators hypothesize that metabolomics profile could represent a potent biomarker of response to ICI

Study Overview

Detailed Description

Immune checkpoints inhibitors (ICI) are becoming new standards of care for Non-Small Cell Lung Carcinoma (NSCLC) treatment, both as first and second line of treatment. To date, no powerful predictive biomarker of response has been found. It has been recently shown that microbiota composition could dictate the ability of patients to respond to ICI. Since, the microbiota produces circulating metabolites that will subsequently act on immune system, the investigators hypothesized that metabolic signature, reflecting microbiota function, could represent a predictive biomarker of response to ICI.

Primary objective is to identify baseline metabolic signature (metabolomics analysis by Mass spectrometry) associated to ICI response. Secondary objectives are to link metabolic signature with microbiota composition (metagenomics analysis RNA 16S) and immune profile, and altogether with clinic response to ICI. Profile evolution (metabolic, metagenomics and immune) will be also analyzed at 2-month post ICI initiation and at tumor progression, if any.

In order to do so, the investigators thus plan to enroll 60 NSCLC patients treated by ICI as 1st, 2nd or 3rd line of treatment in CHUGA in 18 months. Blood as well feces will be collected prior to, and at 2 month following ICI treatment initiation as well as at progression. Will be excluded from this study, patients that have received antibiotic or corticotherapy 2 or 4 weeks before ICI initiation, respectively.

Study Type

Observational

Enrollment (Actual)

62

Contacts and Locations

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

Study Locations

    • Isère
      • La Tronche, Isère, France, 38700
        • University Hospital, Grenoble

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

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study cohort will include NSCLC patients treated by ICI as 1st, 2nd or 3rd line of treatment in Grenoble University Hospital (France) in 18 months. 60 NSCLC patients are anticipated to be enrolled in the study.

Description

Inclusion Criteria:

  • NSCLC diagnosis
  • Patient treated by a ICI in first, second or third line of treatment, or by the combination of chemotherapy and IPCI in first line of treatment
  • Patient with at least one measurable lesion as defined by RECIST

Exclusion Criteria:

  • Patient treated with antibiotic treatment within 2 weeks before the start of ICI or corticosteroids (>20 mg per day) within 4 weeks before the start of ICI

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
First line
20 patients in first line of treatment
Immune signature in serum associated to the metabolic signature
Meta-genomic signature of intestinal flora
Second or third line
40 patients in second and third line of treatment
Immune signature in serum associated to the metabolic signature
Meta-genomic signature of intestinal flora

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of the change from baseline Metabolic signature as predictive factor of the ICI response at 6 months or at the tumoral progression
Time Frame: baseline, 6 months or tumoral progression
To identify the link of the change from baseline of Metabolic signature in serum (metabolomics analysis performed using a Mass spectrometry) and the ICI response at 6 months or at the tumoral progression
baseline, 6 months or tumoral progression

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of the link between the Meta-genomic and immune signatures and the metabolic signature at 6 months or at the tumoral progression
Time Frame: 6 months or tumoral progression
To identify the link between the Meta-genomic signature of intestinal flora (microbiota composition analysed by RNA 16 S) with the Immune signature in serum and the metabolic signature at 6 months or at the tumoral progression
6 months or tumoral progression
Identification of the link between the Meta-genomic and immune signatures and ICI response at 6 months or at the tumoral progression
Time Frame: 6 months or tumoral progression
To identify the link between the Meta-genomic signature of intestinal flora with the Immune signature in serum and the ICI response at 6 months or at the tumoral progression
6 months or tumoral progression
Description of the profile change of Meta-genomic signature
Time Frame: 2 months or tumoral progression
To describe the change from baseline of the Meta-genomic signature at 2 months or at the tumoral progression
2 months or tumoral progression
Description of the profile change of Immune signature at 2 months or at the tumoral progression
Time Frame: Baseline and 2 months or tumoral progression
To describe the change from baseline of the Immune signature at 2 months or at the tumoral progression
Baseline and 2 months or tumoral progression
Identification of the link between the profile change of meta-genomic signature and the ICI response at 2 months or at the tumoral progression
Time Frame: Baseline and (2 months or tumoral progression)
To identify the link between the profile change from baseline of meta-genomic signature and the ICI response at 2 months or at the tumoral progression
Baseline and (2 months or tumoral progression)
Identification of change of immune signature and the ICI response at 2 months or at the tumoral progression
Time Frame: Baseline and (2 months or tumoral progression)
To identify the link between the profile change from baseline of immune signature and the ICI response at 2 months or at the tumoral progression
Baseline and (2 months or tumoral progression)
Description of overall survival under ICI at 6 months or at the tumoral progression
Time Frame: 6 months or tumoral progression
To describe of the overall survival under ICI at 6 months or at the tumoral progression
6 months or tumoral progression
Description of the survival without progression under ICI at 6 months or at the tumoral progression
Time Frame: 6 months or tumoral progression
To describe the survival without progression under ICI at 6 months or at the tumoral progression
6 months or tumoral progression

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Anne-Claire Toffart, Dr, University Hospital, Grenoble
  • Study Director: Dalil Hannani, PhD, Medicine University, Grenoble

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 (Actual)

January 3, 2020

Primary Completion (Actual)

January 27, 2023

Study Completion (Actual)

January 27, 2023

Study Registration Dates

First Submitted

October 3, 2019

First Submitted That Met QC Criteria

December 5, 2019

First Posted (Actual)

December 6, 2019

Study Record Updates

Last Update Posted (Estimated)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 15, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

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