Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy

NCT04487457 | Completed

• 2 other identifiers: RIPH3-RNI20 / CINECI2020-A01478-31
• Study Type: observational
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

Non-small cell lung cancer (NSCLC) is the most common histological form, accounting for 85% of all bronchopulmonary cancers (PBC). The advent of Immunity Checkpoint Inhibitors (ICIs) targeting Programmed cell Death-1 (PD-1) is changing current treatment algorithms. Preliminary results from work carried out in the Medical Oncology Department of the University Hospital of Tours suggest that immunotherapy targeting ICI, when administered beforehand, increases the effect of catch-up chemotherapy. In NSCLC, the progression-free survival (PFS) of 3rd line chemotherapy after anti-PD-1 immunotherapy was better than the PFS of 3rd line chemotherapy performed at the end of conventional chemotherapy. Moreover, the combination of chemotherapy and immunotherapy gives paradoxically better results than immunotherapy alone. Immunotherapy restores the anti-tumor T immunity inhibited by the cancer cell. While the mode of action of ICIs is well known, the mechanisms of resistance to them are poorly understood. Several pathways are evoked, in particular the modulation of cellular interactions within the tumour microenvironment (TME), the molecular expression profile of cancer cells, or the immunological status of the patient. Regulatory T lymphocytes (Treg) participate in the maintenance of immune system homeostasis by ensuring tolerance to self antigens. Within TME, Treg inhibit anti-tumor T cell activity and potentiate tumor proliferation. The latter, by specifically recognizing tumor antigens, block the activity of effector T lymphocytes directed against tumor cells. Thus, an increase in circulating Treg concentrations and in TME is a poor prognostic factor, especially in NSCLC. Gemcitabine chemotherapy is commonly used in the management of NSCLC. Recent data show that gemcitabine decreases Treg activity and regulates levels of anti-inflammatory TME cytokines such as IL10, TGF-β and interferon-Ɣ. The hypothesis of this study is that the decrease in Treg blood concentration by catch-up chemotherapy restores sensitivity to immunotherapy.

Conditions

Non Small Cell Lung Cancer; Bladder Cancer; ENT Cancer

Keywords

Immunity checkpoint inhibitor; Rescue chemotherapy; Non Small Cell Lung Cancer; Bladder Cancer

Outcome Measures

Primary Outcomes (2)

• Change from baseline blood concentration of regulatory T-lymphocytes (Treg) at 6 months

  Blood concentrations will be measured at specific times

  Baseline, 3 months and 6 months

• Change from baseline blood concentration of lymphocyte populations T, B, NK, CD4+ and CD8+ (effector T-lymphocytes (Teff) included) at 6 months

  Blood concentrations will be measured at specific times

  Baseline, 3 months and 6 months

Secondary Outcomes (3)

• Change from baseline blood concentration of anti-inflammatory cytokines at 6 months

  Baseline, 3 months and 6 months

• Assess correlation between blood concentration of Treg, blood concentration of Teff and blood concentration of anti-inflammatory cytokines

  Baseline, 3 months and 6 months

• Determination of PDL1 status

  Baseline

Study Arms (1)

Cancer

Patients receiving chemotherapy alone after immunotherapy for NSCLC or bladder cancer or ENT cancer

Other: Blood samples

Interventions

Blood samples OTHER

Blood samples

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

The study population is patients receiving chemotherapy alone after immunotherapy for NSCLC or bladder cancer or ENT cancer.

You may qualify if:

• Age ≥ 18 years old
• Patients treated with immune checkpoint inhibitor alone or in combination with chemotherapy in 1st or 2nd line
• Patient with locally advanced or metastatic Non-Small-Cell Lung Cancer, or bladder cancer or Ear Nose Throat cancer
• Maximum delay of 2 months between ICI and chemotherapy

You may not qualify if:

• Symptomatic brain metastases
• Corticotherapy \> 10 mg/day
• Active auto-immune disease
• Oncogenic addiction
• Data processing objection

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (2)

Medical oncology department, University Hospital, Tours

Tours, 37044, France

Location

Pneumology department, University Hospital, Tours

Tours, 37044, France

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Urinary Bladder Neoplasms

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

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

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 27, 2020
• Study Start: September 3, 2021
• Primary Completion: September 29, 2022
• Study Completion: September 29, 2022
• Last Updated: April 6, 2023

Record last verified: 2023-04

Locations

FR (2)