Relationship Between Immunity and Metabolism in Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer. ( RIMEC ) (RIMEC)

Assessment of Metabolic and Immune Profiles in Patients Receiving Immune Checkpoint Inhibitors (ICI) for Advanced Renal Cell Carcinoma or Lung Carcinoma.

Recent EMA and FDA approvals have made immune checkpoint inhibitors (ICI) a standard of care in cancer treatment. ICI, used alone or as a combination are now the backbone of renal cell and lung carcinoma treatment. However, a significant proportion of patients does not respond to ICI. Thus the identification of predictive response factor is a major issue.

While factors associated with the tumour and its micro environment have been widely studied, factors associated with the patient such as metabolism could also affect the response to ICI and remain poorly studied.

The hypothesis of the investigators is that dysmetabolims, via the induction of a chronic inflammatory state could induce a defect of lymphocyte production and activation as well as a modification of the immunogenicity of tumor cells and immune cells infiltration. The consequences could be a decrease in ICI response rate as well as an increase in immune related adverse events (irAEs).

To test this hypothesis, the investigators propose a prospective bi-centric exploratory study including 60 patients treated with ICI for advanced lung or renal cell carcinoma.

The data collected will be :

• Clinical (calorimetry, impedancemetry, survey of eating habits, tumour characteristics, epidemiological data),
• Biologics (baseline and 3-months plasma bio banking for standard biology, inflammation markers TNF- α, IL1-6-8-11-17, TGF-ß, TWEAK, complement study C3, C4, C4d, CH50, C1q, CD46)

Primary objective is to assess the response to ICI depending on metabolic status.

Secondary objectives are to study the relationships between metabolism / cytokines profile/ complement profile and ICI response.

The investigators seek to generate hypotheses and to obtain exploratory data before submission of a Hospital Clinical Research Program whose objective will be to evaluate the impact of dysmetabolism on overall survival and to characterize immune and anatomopathological profiles (using DNA microarrays and flow cytometry techinques) of patients treated with ICI for renal cell or lung carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Cancer; Immune Checkpoint Inhibitors; Metabolism Disorder
• Intervention / Treatment: Diagnostic test: calorimetry, impedance measurement at baseline and after 3 months of treatment

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Île-de-France
    • Paris, Île-de-France, France, 75014
      • Hopital Cochin
    • Paris, Île-de-France, France, 75015
      • AP-HP - Hôpital Européen Georges-Pompidou Paris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients ≥18 years
• patients receiving immune checkpoint inhibitors, used alone or as a combination with chemotherapy or tyrosine kinase inhibitor or other immune checkpoint inhibitor, for advanced renal cell or lung carcinoma.
• Patient Informed and signed the consent to participate in the research

Exclusion Criteria:

• patients with history of auto immune disease
• patients enrolled in an interventional study or be in the exclusion period following a previous research, if applicable
• Patient not affiliated to the social security scheme or under AME
• Patient under guardianship or curatorship or under legal protection
• Patient unable or unwilling to give written consent
• Pregnant patient

be in the exclusion period following a previous research, if applicable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patients	Diagnostic test: calorimetry, impedance measurement at baseline and after 3 months of treatment; biobanking (30ml) for cytokines and complement dosages at baseline and after 3 months of treatment calorimetry and impedance measure will be collected at baseline and after 3 months of ICI treatment; Other Names: biobanking (30ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
response rate according to metabolic status	response rate after 6 months of ICI treatment (iRECIST criteria)	6 months from randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 months progression free survival according to metabolic status	6 months progression free survival according to metabolic status	6 months from randomisation
12 months overall survival according to metabolic status	12 months overall survival according to metabolic status	12months from randomisation
correlations between metabolism/ cytokines dosage/ complement dosage and response to ICI	correlations between metabolism/ cytokines dosage/ complement dosage and	12 months from randomisation
incidence of irAEs according to metabolic profile	incidence of irAEs according to metabolic profile	6 months from randomisation

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: SIMONAGGIO Audrey, MD, Hopital Europeen Georges-Pompidou; Principal Investigator: Charles Vauchier, Hopital Europeen Georges-Pompidou

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Actual): April 9, 2024
• Study Completion (Estimated): October 9, 2024

Study Registration Dates

• First Submitted: March 8, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases
• Other Study ID Numbers: APHP201166; IDRCB 2020-A02262-37 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
• IPD Sharing Time Frame: Two years after the last publication

IPD Sharing Access Criteria

Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.

Data sharing must respect the agreements made with funders.

Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement.

Processing of shared data must comply with European General Data Protection Regulation (GDPR).

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No