Metastatic NSCLCMADMASNCT05091190
Immunotherapy Clearance and Phenotype of Circulating Tumor Cells in Lung and Head and Neck Cancers
A study testing Blood draws in people with Metastatic NSCLC and Metastatic Head and Neck Cancer, run by Hospices Civils de Lyon at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic NSCLC, Metastatic Head and Neck Cancer
- What is being tested?
- Blood draws
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 2 sitesFrance
- Study dates
- 27 Oct 2021to 11 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
About this study
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
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.
Read more
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
- Being tested
- Blood draws
- Keywords
- metastatic NSCLC, metastatic head and neck cancer, clearance, PD-L1, CTCs, Immunotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood drawsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Blood draws |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: At the end of cycle 2 (each cycle is 21 days)
Secondary outcomes (7)
Overall survival
time elapsed between the first immunotherapy administration and the death
Measured: 2 years
Progression free survival
time elapsed between the first immunotherapy administration and progression
Measured: 2 years
level of PD-L1 expression on primary tumor tissue
The level of PD-L1 expression will be measured by ICH on tissue from primary tumor surgery/biopsy through study completion, an average of 2 years.
Measured: 2 years
Baseline transcriptomic profile of CTCs isolated form peripheral blood
Baseline transcriptomic profile of CTCs isolated form peripheral blood: the transcriptomic profile of CTCs will be analyzed by NGS (Next-Generation Sequencing) from blood samples collected at cycle 1 day 1, before treatment administration.
Measured: 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
The transcriptomic profile of CTCs will be analyzed by NGS (Next-Generation Sequencing) from blood samples collected after the 1st cycle of treatment (cycle length between 14 and 21 days depending on the type of immunotherapy)
Measured: Day 1 of cycle 2, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
2nd cycle transcriptomic profile of CTCs isolated form peripheral blood
The transcriptomic profile of CTCs will be analyzed by NGS (Next-Generation Sequencing) from blood samples collected at the end of cycle 2 (each cycle is 21 days).
Measured: Day 1 of cycle 3, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
identification of CTCs transcriptomic signatures, associated to immunotherapy efficacy or toxicity
the CTCs transcriptomic profile (measure 4) will be obtained with the NGS method; the analyses of these profiles will imply statistical models of logistic regression (Lasso Method). These data will be compared with clinical data on efficacy (PFS measured at 2 years after the beginning of treatment) and toxicity (stopping treatment for toxicity before the third cycle).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2021
- Study start27 Oct 2021
- Primary completion11 Dec 2026 (estimated)
- Study completion11 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic NSCLCStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre PHILOUZE, MD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05091190
- Sponsor's protocol ID
- 69HCL21_0458
- Other IDs
- 2021-A01482-39
- Acronym
- MADMAS
- Status last verified
- Sep 2025
- First submitted
- 1 Sep 2021
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05091190
- Acronym / sponsor ID
- MADMAS / 69HCL21_0458
- Conditions
- Metastatic NSCLC, Metastatic Head and Neck Cancer
- Keywords
- metastatic NSCLC, metastatic head and neck cancer, clearance, PD-L1, CTCs, Immunotherapy
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 27 Oct 2021 (actual)
- Primary completion
- 11 Dec 2026 (estimated)
- Study completion
- 11 Dec 2026 (estimated)
- First posted
- 25 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cancer patients | Other | Other: Blood drawsMADMAS 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood drawsBlood 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. | Other | cancer patients |
Primary outcome
Immunotherapy clearance (mL/min) and number of PD-L1 (absolute number) positive CTCs after two cycles of treatment (composite criteria)
Time frame: At the end of cycle 2 (each cycle is 21 days)
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).
7 secondary outcomes
Overall survival
Time frame: 2 years
Progression free survival
Time frame: 2 years
level of PD-L1 expression on primary tumor tissue
Time frame: 2 years
Baseline transcriptomic profile of CTCs isolated form peripheral blood
Time frame: 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
Time frame: Day 1 of cycle 2, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
2nd cycle transcriptomic profile of CTCs isolated form peripheral blood
Time frame: Day 1 of cycle 3, before treatment administration (cycle length: 14 days for nivolumab treatment and 21 days for pembrolizumab treatment)
identification of CTCs transcriptomic signatures, associated to immunotherapy efficacy or toxicity
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre PHILOUZE, MD principal investigator
Hospices Civils de Lyon
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood draws in people with Metastatic NSCLC and Metastatic Head and Neck Cancer, run by Hospices Civils de Lyon at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immunotherapy clearance (mL/min) and number of PD-L1 (absolute number) positive CTCs after two cycles of treatment (composite criteria) (time frame: At the end of cycle 2 (each cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.