Clinical trial NCT05091190: Immunotherapy Clearance and Phenotype of Circulating Tumor Cells in Lung and Head and Neck Cancers
Official title: Immunotherapy Clearance and Phenotype of Circulating Tumor Cells in Patients With Lung and Head and Neck Cancers, Treated With an Immunotherapy-based Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic NSCLC
Metastatic Head and Neck Cancer
Keywords: metastatic NSCLC
metastatic head and neck cancer
clearance
PD-L1
CTCs
Immunotherapy
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2021-10-25
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

Lung cancer (n= 30):

* Adult patients
* Patients who gave its written informed consent to participate to the study
* Weight at inclusion ≥ 48 kg
* 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
* PD-L1 status on primary tumor available at the inclusion
* 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
* Weight at inclusion ≥ 48 kg
* 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)
* PD-L1 status on primary tumor available at the inclusion
* Patients affiliated to a social insurance regime

Exclusion Criteria:

* 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

Exclusion Criteria specific pour head and neck cohort:

- Patients already treated with immunotherapy

Primary outcomes:
measure: Immunotherapy clearance (mL/min) and number of PD-L1 (absolute number) positive CTCs after two cycles of treatment (composite criteria)
timeFrame: At the end of cycle 2 (each cycle is 21 days)
Secondary outcomes:
measure: Overall survival
timeFrame: 2 years
measure: Progression free survival
timeFrame: 2 years
measure: level of PD-L1 expression on primary tumor tissue
timeFrame: 2 years
measure: Baseline transcriptomic profile of CTCs isolated form peripheral blood
timeFrame: Day 1 of cycle 1, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
measure: 1st cycle transcriptomic profile of CTCs isolated form peripheral blood
timeFrame: Day 1 of cycle 2, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
measure: 2nd cycle transcriptomic profile of CTCs isolated form peripheral blood
timeFrame: Day 1 of cycle 3, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
measure: identification of CTCs transcriptomic signatures, associated to immunotherapy efficacy or toxicity
timeFrame: 2 years
Other outcomes:
Locations:
city: Lyon
country: France
facility: Croix Rousse Hospital
city: Pierre-Bénite
country: France
facility: Lyon Sud Hospital
Study officials:
affiliation: Hospices Civils de Lyon
name: Pierre PHILOUZE, MD
role: PRINCIPAL_INVESTIGATOR
References: