Immunotherapy Clearance and Phenotype of Circulating Tumor Cells in Lung and Head and Neck Cancers

NCT05091190 | Active Not Recruiting

• 2 other identifiers: 69HCL21_04582021-A01482-39
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 2

Brief Summary

Immunotherapy is widely administrated as anticancer treatment in metastatic setting. Despite a proved efficacy in several cancer types and clinical situations, it exists a wide variability of responses in terms of efficacy and toxicity. The rate of responders depends mostly on the type of pathology, with 40% of responders among melanoma patients, 20-30% among lung and head and neck cancer patients and only 1% of responders among pancreatic cancer patients. Thus, the main challenge today is to be able to select patients for whom the treatment is likely to be effective. Several studies suggested that tumors with a high mutational burden and expressing PD-L1 are better responders to immunotherapy. However, a proportion of PD-L1 negative cancers responds to immunotherapy, suggesting that other parameters have to be considered together with PD-L1 expression. Of that, the immunotherapy clearance seems to have an impact on overall survival, but larger studies, including different molecules and cancer types, are needed to better understand the correlation between the clearance and the response to immunotherapy. Tumor cells released from the primary tumor in the blood circulation (CTCs, for circulating tumor cells) are considered as "liquid biopsies", as they contain the entire genetic and phenotypic information representative of the tumor, including PD-L1 expression. Thus, the variation of PD-L1 expression under treatment can be easily followed-up on blood samples collected during the time. The objective of MADMAS is to study the correlation between the immunotherapy clearance, measured at the different times during treatment, and the variation of the number of CTCs expressing PD-L1 after two cures of treatment. MADMAS will enroll patients with lung or head and neck cancers, treated with an immunotherapy-based therapy. Blood samples will be collected at the baseline and before the first two cures of treatment. The immunotherapy clearance will be measured with an innovative approach of Mass Spectrometry, and PD-L1 expression will be measured on CTCs, purified with a highly sensitive microfluidics technology.

Conditions

Metastatic NSCLC; Metastatic Head and Neck Cancer

Keywords

metastatic NSCLC; metastatic head and neck cancer; clearance; PD-L1; CTCs; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Immunotherapy clearance (mL/min) and number of PD-L1 (absolute number) positive CTCs after two cycles of treatment (composite criteria)

  The clearance and the number of PD-L1 positive cells will be measured on blood samples collected the day of the third immunotherapy administration (each cycle is 14 to 28 days, depending on the type of immunotherapy).

  At the end of cycle 2 (each cycle is 21 days)

Secondary Outcomes (7)

• Overall survival

  2 years

• Progression free survival

  2 years

• level of PD-L1 expression on primary tumor tissue

  2 years

• Baseline transcriptomic profile of CTCs isolated form peripheral blood

  Day 1 of cycle 1, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)

• 1st cycle transcriptomic profile of CTCs isolated form peripheral blood

  Day 1 of cycle 2, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)

Study Arms (1)

cancer patients

OTHER

MADMAS will include 30 patients with metastatic NSCLC and 30 patients with metastatic head and neck cancers; patients will NSCLC will receive an immunotherapy-based treatment in first line metastatic setting; patients with head and neck cancers are included if they are planned to receive an immunotherapy-based treatment, whatever the line.

Other: Blood draws

Interventions

Blood draws OTHER

Blood draws will be realized at the following time points: C1T1: at the baseline, before treatment administration. C1T2: cycle 1, after treatment administration. C2T1: the day of the 2nd cycle, before treatment administration. C2T2: the day of 2nd cycle, after treatment administration. C3T1: the day of the 3rd cycle, before treatment administration. C3T2: the day of 3rd cycle, after treatment administration.

cancer patients

Eligibility Criteria

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

You may qualify if:

• Lung cancer (n= 30):
• Adult patients
• Patients who gave its written informed consent to participate to the study
• NSCLC histology only
• Stage IV according to 8th TNM classification
• Planned to be treated with immunotherapy (+/- chemotherapy) as a first line treatment in metastatic setting
• Patients affiliated to a social insurance regime
• Head and neck cancer (n= 30):
• Adult patients
• Patients who gave its written informed consent to participate to the study
• Recurrent or metastatic epidermoid carcinomas from oral cavity, oropharynx, hypopharynx, larynx (except nasopharynx)
• Stage IV according to 8th TNM classification
• Planned to be treated with immunotherapy (+/- chemotherapy)
• Patients affiliated to a social insurance regime

You may not qualify if:

• History of previous cancers, except for adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, treated and with no evidence of disease for ≥ 5 years
• Patients under tutorship or guardianship
• Pregnant or breast feeding women
• Patients under psychiatric care
• \- Patients already treated with immunotherapy

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Croix Rousse Hospital

Lyon, France

Location

Lyon Sud Hospital

Pierre-Bénite, France

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Head and Neck 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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Pierre PHILOUZE, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: October 25, 2021
• Study Start: October 27, 2021
• Primary Completion (Estimated): December 11, 2026
• Study Completion (Estimated): December 11, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)