Response and Toxicity Prediction by Microbiome Analysis After (Concurrent) Chemoradiotherapy

NCT04711330 | Active Not Recruiting

• 1 other identifier: 76017
• Study Type: observational
• Target: 126
• Locations: 2 countries
• Sites: 6

Brief 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. 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.

Conditions

Non Small Cell Lung Cancer Stage III; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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

  1 year

Secondary Outcomes (4)

• Prediction of toxicity based on microbiome analysis

  1 year

• Prediction of outcome (disease controle rate) based on microbiome analysis

  1 year

• Relationship between circulating immune cells and microbiome outcome

  1 year

• Value of analysis of exhaled breath at 6 months

  6 months

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Leiden University Medical Center: lead
• The Netherlands Cancer Institute: collaborator
• Jessa Hospital: collaborator

Study Sites (6)

Kristof Cuppens

Hasselt, Flanders, 3500, Belgium

Location

Piet Verkouteren

Aalst, B-9300, Belgium

Location

Ingel Demedts

Roeselare, B8800, Belgium

Location

Lynn Decoster

Turnhout, B2300, Belgium

Location

Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

Location

Leiden University Medical center

Leiden, 2333ZA, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

Collection of bacterial specimen from throat and feces.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Paul Baas, MD PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 15, 2021
• Study Start: September 1, 2022
• Primary Completion: October 1, 2025
• Study Completion: October 2, 2025
• Last Updated: October 6, 2025

Record last verified: 2025-03

Locations

NL (2); BE (4)