Clinical trial NCT04189679: Identification of a Predictive Metabolic Signature of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Carcinoma
Official title: : Identification of a Predictive Metabolic Signature of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Carcinoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non Small Cell Lung Cancer
Keywords: Metabolomic
Microbiota
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2019-12-06
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of the change from baseline Metabolic signature as predictive factor of the ICI response at 6 months or at the tumoral progression
timeFrame: baseline, 6 months or tumoral progression
Secondary outcomes:
measure: Identification of the link between the Meta-genomic and immune signatures and the metabolic signature at 6 months or at the tumoral progression
timeFrame: 6 months or tumoral progression
measure: Identification of the link between the Meta-genomic and immune signatures and ICI response at 6 months or at the tumoral progression
timeFrame: 6 months or tumoral progression
measure: Description of the profile change of Meta-genomic signature
timeFrame: 2 months or tumoral progression
measure: Description of the profile change of Immune signature at 2 months or at the tumoral progression
timeFrame: Baseline and 2 months or tumoral progression
measure: Identification of the link between the profile change of meta-genomic signature and the ICI response at 2 months or at the tumoral progression
timeFrame: Baseline and (2 months or tumoral progression)
measure: Identification of change of immune signature and the ICI response at 2 months or at the tumoral progression
timeFrame: Baseline and (2 months or tumoral progression)
measure: Description of overall survival under ICI at 6 months or at the tumoral progression
timeFrame: 6 months or tumoral progression
measure: Description of the survival without progression under ICI at 6 months or at the tumoral progression
timeFrame: 6 months or tumoral progression
Other outcomes:
Locations:
city: La Tronche
country: France
facility: University Hospital, Grenoble
state: Isère
Study officials:
affiliation: University Hospital, Grenoble
name: Anne-Claire Toffart, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Medicine University, Grenoble
name: Dalil Hannani, PhD
role: STUDY_DIRECTOR
References: