## Protocol Section
### Identification Module
**NCT ID:** NCT04189679

**Acronym:** METABO-ICI

**Brief Title:** 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

#### Organization Study ID Info
**ID:** 38RC19.133
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Grenoble
#### Secondary ID Infos
**Domain:** ID RCB
**ID:** 2019-A01255-52
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2023-01-27

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-01-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-01-15

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2023-01-27

**Type:** ACTUAL

#### Start Date
**Date:** 2020-01-03

**Type:** ACTUAL

**Status Verified Date:** 2024-01

#### Study First Post Date
**Date:** 2019-12-06
**Type:** ACTUAL
**Study First Submit Date:** 2019-10-03
**Study First Submit QC Date:** 2019-12-05
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Grenoble

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Non Small Cell Lung Cancer

**Keywords:**

- Metabolomic

- Microbiota

### Design Module

#### Bio Spec

**Description:** Meta-genomic signature of intestinal flora

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 62

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 20 patients in first line of treatment

**Intervention Names:**

- Other: Immune signature in serum associated to the metabolic signature

- Genetic: Meta-genomic signature of intestinal flora

**Label:** First line

#### Arm Group 2

**Description:** 40 patients in second and third line of treatment

**Intervention Names:**

- Other: Immune signature in serum associated to the metabolic signature

- Genetic: Meta-genomic signature of intestinal flora

**Label:** Second or third line

### Interventions

#### Intervention 1

**Arm Group Labels:**

- First line

- Second or third line

**Description:** Immune signature in serum associated to the metabolic signature

**Name:** Immune signature in serum associated to the metabolic signature

**Type:** OTHER

#### Intervention 2

**Arm Group Labels:**

- First line

- Second or third line

**Description:** Meta-genomic signature of intestinal flora

**Name:** Meta-genomic signature of intestinal flora

**Type:** GENETIC

### Outcomes Module

#### Primary Outcomes

**Description:** 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

**Measure:** 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

#### Secondary Outcomes

**Description:** 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

**Measure:** 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

**Description:** 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

**Measure:** 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

**Description:** To describe the change from baseline of the Meta-genomic signature at 2 months or at the tumoral progression

**Measure:** Description of the profile change of Meta-genomic signature

**Time Frame:** 2 months or tumoral progression

**Description:** To describe the change from baseline of the Immune signature at 2 months or at the tumoral progression

**Measure:** 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

**Description:** 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

**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

**Time Frame:** Baseline and (2 months or tumoral progression)

**Description:** 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

**Measure:** 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)

**Description:** To describe of the overall survival under ICI at 6 months or at the tumoral progression

**Measure:** Description of overall survival under ICI at 6 months or at the tumoral progression

**Time Frame:** 6 months or tumoral progression

**Description:** To describe the survival without progression under ICI at 6 months or at the tumoral progression

**Measure:** Description of the survival without progression under ICI at 6 months or at the tumoral progression

**Time Frame:** 6 months or tumoral progression

### Eligibility Module

**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

**Maximum Age:** 100 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**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.

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** La Tronche

**Country:** France

**Facility:** University Hospital, Grenoble

**State:** Isère

**Zip:** 38700

#### Overall Officials

**Official 1:**

**Affiliation:** University Hospital, Grenoble

**Name:** Anne-Claire Toffart, Dr

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Medicine University, Grenoble

**Name:** Dalil Hannani, PhD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009369

- Term: Neoplasms

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M11172

- Name: Lung Neoplasms

- Relevance: HIGH

- As Found: Lung Carcinoma

- ID: M5546

- Name: Carcinoma, Non-Small-Cell Lung

- Relevance: HIGH

- As Found: Non-Small Cell Lung Carcinoma

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002289

- Term: Carcinoma, Non-Small-Cell Lung

- ID: D000008175

- Term: Lung Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M2342

- Name: Immune Checkpoint Inhibitors

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
