Non Small Cell Lung Cancer Stage IIIPredictionNCT04711330
Response and Toxicity Prediction by Microbiome Analysis After (Concurrent) Chemoradiotherapy
An observational study of Non Small Cell Lung Cancer Stage III and Immunotherapy, run by Leiden University Medical Center at 6 sites in 2 countries.
Trial summary
The predictive value of the microbiome (throat swabs, stool and of bronchial samples) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer Stage III, Immunotherapy
- How many people
- 126 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 1 Sep 2022to 2 Oct 2025
- How long will I take part?
- 1 Year
- Phase
- Observational
- 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
- Adult, Older adult
Study population: All patients who will receive durvalumab as standard of care after completion of (concurrent) chemo-radiation therapy for stage III non small cell lung cancer
Who may be able to join
- Stages IIIA, IIIB and IIIC (as per UICC 8th TNM edition) NSCLC (histologically or cytologically confirmed) amenable for durvalumab treatment after sequential or concurrent chemoradiotherapy according to local standards. Patients that received neoadjuvant/adjuvant chemotherapy for surgically treated stages I to III NSCLC are allowed as long as therapy was completed at least 6 months prior to the diagnosis of disease recurrence amenable for chemoradiotherapy and resolution of all treatment related toxicity ≤ grade 1 .
- No signs of disease progression after CCRT
- At least 1 cycle of chemotherapy before or concurrent during radiotherapy but no more chemotherapy between last radiotherapy session and start durvalumab
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Absence of any of following targetable driver mutations: EGFR, ALK, ROS1
- over 18 years
Show all 9Show fewer
- ECOG 0-1
- Must be willing to provide collected stool samples and allow to obtain a throat swab during the observation period. A pulmonary protected brush swab will only be optionally performed in a selected number of patients.
- Demonstrate adequate organ function
Who cannot join
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has had prior monoclonal antibody therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Previous treatment with PD-1-PD-L1 axis inhibiting immunotherapy.
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:
- Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
Show all 18Show fewer
- Skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic immunosuppressive treatment, in particular corticosteroids are permitted to enrol.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Subjects who have undergone organ transplant or allogeneic stem cell transplantation.
- Active malignancy or a prior malignancy within the past 3 years, with the following exceptions:
- Patients with completely resected basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and patients with isolated elevation in prostate-specific antigen or low risk prostate cancer (managed with watchful waiting) are allowed.
- Patients who underwent mediastinal radiotherapy in the past are not allowed.
- Subjects with chronic infections/infectious disorders (eg. Clostridium colitis)
- Have known but untreated driver mutations of the EGFR gene or ALK or ROS1 translocation.
- Has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis.
- Has an active chronic infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Belgium4 sites
Piet Verkouteren
Aalst, B-9300
Kristof Cuppens
Hasselt, Flanders, 3500
Ingel Demedts
Roeselare, B8800
Lynn Decoster
Turnhout, B2300
Netherlands2 sites
Netherlands Cancer Institute
Amsterdam, 1066CX
Leiden University Medical center
Leiden, 2333ZA
About this study
Official title: Response and Toxicity Prediction by Microbiome Analysis After (Concurrent) Chemo RT in Locally Advanced NSCLC Treated With IO (Durvalumab)
The predictive value of the microbiome (throat swabs, stool and of bronchial samples) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months. Exploratory endpoints include the effects of antibiotic therapy before and during IO treatment on toxicity and response rate. The role of exhaled breath analysis in prediction of response and toxicity will also be investigated.
Read the detailed description
In this observational study we aim to investigate the predictive value of the microbiome (throat swabs and stool) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months.
Collection of stool and throat swipe before start of durvalumab treatment; sampling of blood and exhaled air for analysis of volatile organic compounds.
Improved clinical outcomes after adjuvant treatment with durvalumab following concurrent chemoradiotherapy (CCRT) for locally advanced NSCLC (PACIFIC trial), led to the rapid adoption of this treatment strategy as standard of care. However, despite the improved progression free survival and overall survival, recurrence rate remains high. Approximately 45% of patients will relapse within 1 year, despite adjuvant durvalumab therapy. To date no performant biomarker predicting treatment response or failure nor toxicity exists and the number of prospective studies addressing this issue is limited. Both PD-L1 TPS and TMB should be considered 'enriching' parameters improving response-chances, but they are far from an ideal biomarker. Non-invasive biomarkers are essential in the future for better patient selection and therapy allocation. One of the potential non-invasive biomarkers of interest is the microbiome.
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients treated with maintenance immunotherapy after concurrent chemo/RT | Observation of response and response. The microbiome of the patients throat and stool will be analyzed before the standard treatment with IO is initiated after completion of the chemoradiation therapy. No intervention is planned. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prediction of outcome (progression) based on microbiome analysis
To investigate the predictive value of the microbiome (throat swabs and stool) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months
Measured: 1 year
Secondary outcomes (4)
Prediction of toxicity based on microbiome analysis
To investigate the predictive value of the microbiome (throat swabs and stool ) to identify patients that develop irAE's during durvalumab treatment after CRT.
Measured: 1 year
Prediction of outcome (disease controle rate) based on microbiome analysis
To determine disease control rate (DCR ie. Stable disease, partial response, and complete response) and PFS at 6 months and correlate to the microbiome.
Measured: 1 year
Relationship between circulating immune cells and microbiome outcome
To investigate to what extend cytological characteristics of circulating immune cells obtained from responders and non-responders differ and to explore to what extend these differences relate to the microbiome.
Measured: 1 year
Value of analysis of exhaled breath at 6 months
To investigate the predictive value of exhaled breath analysis (by eNose) to identify patients who will relapse or progress during durvalumab treatment after CRT (False negative Rate) at 6 months.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2021
- Study start1 Sep 2022
- Primary completion1 Oct 2025 (estimated)
- Study completion2 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung Cancer Stage IIIStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 126 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Netherlands Cancer Institute, Jessa Hospital
- Responsible party
- Principal investigator, pbaas, Leiden University Medical Center
- Investigators
- Paul Baas, MD PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04711330
- Sponsor's protocol ID
- 76017
- Acronym
- Prediction
- Status last verified
- Mar 2025
- First submitted
- 12 Jan 2021
- Last updated
- 6 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: microbioma data from the participants
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response and Toxicity Prediction by Microbiome Analysis After (Concurrent) Chemo RT in Locally Advanced NSCLC Treated With IO (Durvalumab)
- ClinicalTrials.gov ID
- NCT04711330
- Acronym / sponsor ID
- Prediction / 76017
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- The Netherlands Cancer Institute, Jessa Hospital
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 2 Oct 2025 (estimated)
- First posted
- 15 Jan 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.
The predictive value of the microbiome (throat swabs, stool and of bronchial samples) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months. Exploratory endpoints include the effects of antibiotic therapy before and during IO treatment on toxicity and response rate. The role of exhaled breath analysis in prediction of response and toxicity will also be investigated.
Detailed description
In this observational study we aim to investigate the predictive value of the microbiome (throat swabs and stool) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months.
Collection of stool and throat swipe before start of durvalumab treatment; sampling of blood and exhaled air for analysis of volatile organic compounds.
Improved clinical outcomes after adjuvant treatment with durvalumab following concurrent chemoradiotherapy (CCRT) for locally advanced NSCLC (PACIFIC trial), led to the rapid adoption of this treatment strategy as standard of care. However, despite the improved progression free survival and overall survival, recurrence rate remains high. Approximately 45% of patients will relapse within 1 year, despite adjuvant durvalumab therapy. To date no performant biomarker predicting treatment response or failure nor toxicity exists and the number of prospective studies addressing this issue is limited. Both PD-L1 TPS and TMB should be considered 'enriching' parameters improving response-chances, but they are far from an ideal biomarker. Non-invasive biomarkers are essential in the future for better patient selection and therapy allocation. One of the potential non-invasive biomarkers of interest is the microbiome.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients treated with maintenance immunotherapy after concurrent chemo/RT | – | –Observation of response and response. The microbiome of the patients throat and stool will be analyzed before the standard treatment with IO is initiated after completion of the chemoradiation therapy. No intervention is planned. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- All patients who will receive durvalumab as standard of care after completion of (concurrent) chemo-radiation therapy for stage III non small cell lung cancer
Key inclusion criteria (9 listed)
- Stages IIIA, IIIB and IIIC (as per UICC 8th TNM edition) NSCLC (histologically or cytologically confirmed) amenable for durvalumab treatment after sequential or concurrent chemoradiotherapy according to local standards. Patients that received neoadjuvant/adjuvant chemotherapy for surgically treated stages I to III NSCLC are allowed as long as therapy was completed at least 6 months prior to the diagnosis of disease recurrence amenable for chemoradiotherapy and resolution of all treatment related toxicity ≤ grade 1 .
- No signs of disease progression after CCRT
- At least 1 cycle of chemotherapy before or concurrent during radiotherapy but no more chemotherapy between last radiotherapy session and start durvalumab
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Absence of any of following targetable driver mutations: EGFR, ALK, ROS1
Key exclusion criteria (18 listed)
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has had prior monoclonal antibody therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Previous treatment with PD-1-PD-L1 axis inhibiting immunotherapy.
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis with the following exceptions:
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prediction of outcome (progression) based on microbiome analysis
Time frame: 1 year
To investigate the predictive value of the microbiome (throat swabs and stool) to identify patients who will relapse during durvalumab treatment after CRT (False negative Rate) at 6 months
4 secondary outcomes
Prediction of toxicity based on microbiome analysis
Time frame: 1 year
Prediction of outcome (disease controle rate) based on microbiome analysis
Time frame: 1 year
Relationship between circulating immune cells and microbiome outcome
Time frame: 1 year
Value of analysis of exhaled breath at 6 months
Time frame: 6 months
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 6 Oct 2025.
- Individual participant dataSharing planned: Undecided. microbioma data from the participants
Related trials for Non Small Cell Lung Cancer Stage III
Recruiting
Understanding the Feasibility of a Co-designed Pre-radiotherapy Exercise Programme - A Single-arm Study
Lung Cancer
RecruitingPhase 2
Adjuvant ctDNA-Adapted Personalized Treatment in Early Stage NSCLC (ADAPT-E)
Non-small Cell Lung Cancer, Non-small Cell Lung Cancer Stage I
RecruitingPhase 3
Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-small Cell Lung Cancer, an ALCHEMIST Treatment Trial (Chemo-IO [ACCIO])
Lung Non-Small Cell Carcinoma, Lung Non-Small Cell Squamous Carcinoma
RecruitingPhase 3
A Global Phase III Study of Rilvegostomig or Pembrolizumab Plus Chemotherapy for First-Line Treatment of Locally Advanced or Metastatic Squamous Non-small Cell Lung Cancer (NSCLC)
Non-small Cell Lung Cancer
RecruitingPhase 3
Chemotherapy Combined With Immunotherapy Versus Immunotherapy Alone for Older Adults With Stage IIIB-IV Lung Cancer, The ACHIEVE Trial
Advanced Lung Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8
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.
Paul Baas, MD PhD principal investigator
Leiden University Medical Center
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non Small Cell Lung Cancer Stage III and Immunotherapy, run by Leiden University Medical Center at 6 sites in 2 countries.
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 9 inclusion and 18 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 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Belgium, Netherlands. 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?
Prediction of outcome (progression) based on microbiome analysis (time frame: 1 year). 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 6 Oct 2025.