PDL-1 Expression on Circulating Tumor Cells in Non-small Cell Lung Cancer

NCT02827344 | Completed

• 1 other identifier: 15 7737 02
• Study Type: observational
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

Immunotherapy is probably, since the development of therapies targeting EGFR mutations or ALK rearrangement, the most attractive therapeutic perspective in the management of metastatic lung cancer. Among the compounds tested, the inhibitors of the immune checkpoint PROGRAMME DEATH 1 / PROGRAMME DEATH LIGAND 1 (PD-1/PD-L1) have been tested in numerous clinical trials with recently published positive results leading to the approval of one drug in the USA and an expanded access program for two drugs in France. PROGRAMME DEATH LIGAND 1 (PD-L1) expression by tumor cells is strongly associated with the response to such molecules so that the participation in various clinical trials is currently reserved for patients expressing this biomarker and therefore justifies a new invasive biopsy (bronchoscopic or CT-guided) representing a considerable drag on the access to these treatments. Circulating tumor cells (CTCs) isolated by Isolation by Size of Tumor Cells (ISET) offer a direct and non-invasive access to the tumor. It has already been demonstrated that molecular characterization (EGFR, ALK) on these blood samples is possible. We propose to demonstrate the feasibility of the analysis PDL-1 expression in these cells by immunocytochemistry. Myeloid-Derived Suppressor Cells (MDSCs) are immature myeloid cells that inhibit T cell functions and thus promote tumor growth. These cells frequently express PD-L1. We propose to test whether MDSCs level and its evolution during treatment with PD1 inhibitor is correlated to the response to these drugs. The main objective of this study is to demonstrate the feasibility of the analysis of PD-L1 expression on CTC

Conditions

Lung Cancer

Keywords

PD-1/PD-L1; Immune checkpoints; Immunotherapy; lung cancer; circulating tumor cells; immunocytochemistry; ISET; MDSC; Stage IV non-small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• Feasibility of analysis of PDL-1 expression on circulating tumor cells as assessed by immunocytochemistry analysis

  Prior to immunotherapy, after four cycle of immunotherapy

  Through the end of study (12 months)

Secondary Outcomes (2)

• Percentage of CTC expressing PD-L1 after four cycle of immunotherapy as assessed by immunocytochemistry analysis

  Through the end of study (12 months)

• Evolution of MDSCs count in response to treatment as assessed by MDSCs analysis

  Through the end of study (12 months)

Study Arms (1)

Stage IV non-small cell lung cancer

Intervention to be done are : \- Blood sample collection for CTC and MDSC analysis

Biological: blood sample collection for CTC and MDSC analysis

Interventions

blood sample collection for CTC and MDSC analysis BIOLOGICAL

* Isolation of circulating tumor cells from 2 tubes by ISET filtration module. Peripheral blood samples will be collected for CTC analysis within 7 days before commencing treatment (defined as baseline) and following four cycles of immunotherapy, * Analysis of PD-L1 and PD-L2 expression by immunocytochemistry on CTC * Analysis of the expression of PD-L1, PD-L2 , CTLA4 on the histological specimen by immunohistochemistry

Stage IV non-small cell lung cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Stage IV non small lung cancer patients

You may qualify if:

• Stage IV non-small cell lung cancer patient prior to start immunotherapy treatment
• Patients with World Health Organization (WHO) performance status 0-3
• Patients who were informed and had non opposition form signed by investigator
• Patients with healthcare insurance system affiliation

You may not qualify if:

• Prior malignancy within 5 years of study entry
• Refusal to participate
• Patient under legal protection

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Larrey Hospital

Toulouse, 31059, France

Location

Related Publications (2)

• Guibert N, Jones G, Beeler JF, Plagnol V, Morris C, Mourlanette J, Delaunay M, Keller L, Rouquette I, Favre G, Pradines A, Mazieres J. Targeted sequencing of plasma cell-free DNA to predict response to PD1 inhibitors in advanced non-small cell lung cancer. Lung Cancer. 2019 Nov;137:1-6. doi: 10.1016/j.lungcan.2019.09.005. Epub 2019 Sep 6.

  PMID: 31518912 RESULT

• Guibert N, Pradines A, Favre G, Mazieres J. [Finding mutations of interest in circulating tumor DNA helps predict immunotherapy response in lung cancer]. Med Sci (Paris). 2020 May;36(5):437-439. doi: 10.1051/medsci/2020068. Epub 2020 May 26. No abstract available. French.

  PMID: 32452359 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

* Peripheral blood sample * Circulating tumor cells isolated from peripheral blood sample * MDSCs : immature myeloid cells that inhibit T cell functions rate analysis from peripheral blood sample * Tissue

MeSH Terms

Conditions

Lung Neoplasms; Neoplastic Cells, Circulating; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Nicolas GUIBERT, PH

  University Hospital of Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2016
• First Posted: July 11, 2016
• Study Start: October 1, 2015
• Primary Completion: October 1, 2021
• Study Completion: December 1, 2021
• Last Updated: August 29, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)