Influence of Biopsy Technique on Moleculargenetic Tumor Characterisation in NSCLC

Study Overview
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Brief Summary
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Study design Prospective multicentre explorative randomized single blinded study to evaluate accuracy of molecular genetic characterisation of NSCLC. Patients with suspected lung cancer are randomized in a 1:1-setting for bronchoscopic tumor tissue either by forceps or by cryobiopsy. Apart from the bronchoscopic techniques liquid biopsy of peripheral blood and if feasible transbronchial needle aspiration with or without endobronchial ultrasound guidance are performed for in all patients. Objectives Primary Objective: assessment of differences in detection of molecular genetic alterations in NSCLC between bronchoscopic forceps biopsy and bronchoscopic cryobiopsy Secondary Objective: assessment of differences in detection of molecular genetic alterations in NSCLC between liquid biopsy, solid tumor tissue by bronchoscopic techniques, cytologic material by TBNA combination of methods (tissue biopsy, TBNA and liquid biopsy) and single techniques naïve and processed tumor tissue specimen (eg. microdissection) To assess differences in side effects e.g. periinterventional bleeding Explorative Objective: To explore tumor mutational burden with regard to solid tumor tissue by bronchoscopic forceps biopsy by bronchoscopic cryobiopsy cytologic material by (EBUS-guided) TBNA liquid biopsy Target subject population Patients with suspected lung cancer or proven NSCLC and visible tumor suspicious lesion(s) requiring tissue diagnosis form the study population of this trial.

Official Title
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A Prospective, Randomized, Single Blinded Multicentre Trial to Evaluate Molecular Genetic Characterisation of Primary Diagnosed or Relapsed Non Small Cell Lung Cancer by Single or Combination of Diagnostic Procedures

Conditions
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Carcinoma, Non-Small-Cell Lung, Pathology, Molecular

Intervention / Treatment
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* Procedure: Forceps biopsy
* Procedure: Cryobiopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent to the study and the study specific procedures prior to any study intervention Male or female patients aged ≥18 years Patients with primary diagnosis of suspected lung cancer OR Patients with known NSCLC and suspected relapse after therapy Bronchoscopically visible tumor Exclusion Criteria: Preexisting malignancy other than NSCLC Contraindication for bronchoscopy according to the international guidelines, daily clinical practice and the local regulations with Patients with existing or at risk of pulmonary and cardiovascular decompensation Patients at increased risk of bleeding with antiplatelet agents except of aspirin (clopidogrel, ticlopidine, …) , anticoagulant therapy (prolonged PTT), thrombocytopenia (< 50.000/ul) or coagulopathy (prolonged in vitro bleeding time). Intolerance to sedation Unstable or immobile cervical spine Limited motion of the temporomandibular joint Previous enrolment in the present study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Forceps group<br> | Procedure: Forceps biopsy<br>* Endobronchial biopsy with the forceps<br>|
| Experimental: Cryobiopsy group<br> | Procedure: Cryobiopsy<br>* Endobronchial biopsy with the cryobiopsy probe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of at least one molecular and/ or genetic alteration. | assessment of differences in detection of molecular genetic alterations in NSCLC between bronchoscopic forceps biopsy and bronchoscopic cryobiopsy | recruiting period approximately 24 months | 
| Differences in the detection of total mutational burden between both techniques. | assessment of differences in detection of molecular genetic alterations in NSCLC between bronchoscopic forceps biopsy and bronchoscopic cryobiopsy | recruiting period approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of any molecular and/ or genetic alterations | assessment of differences in detection rate of molecular genetic alterations in NSCLC between different bronchoscopic (forceps/ cryobiopsy) specimens (No 1 to No 4) liquid biopsy, solid tumor tissue by bronchoscopic techniques, cytologic material by TBNA combination of methods (tissue biopsy, TBNA and liquid biopsy) and single techniques naïve and processed tumor tissue specimen (eg. microdissection) To assess differences in side effects e.g. periinterventional bleeding | recruiting period approximately 24 months | 
| Combinations of molecular and/ or genetic alterations | assessment of differences in detection rate of molecular genetic alterations in NSCLC between different bronchoscopic (forceps/ cryobiopsy) specimens (No 1 to No 4) liquid biopsy, solid tumor tissue by bronchoscopic techniques, cytologic material by TBNA combination of methods (tissue biopsy, TBNA and liquid biopsy) and single techniques naïve and processed tumor tissue specimen (eg. microdissection) To assess differences in side effects e.g. periinterventional bleeding | recruiting period approximately 24 months | 
| Differences in the quantity of total mutational burden between the different techniques | assessment of differences in the quantity of total mutational burden between different bronchoscopic (forceps/ cryobiopsy) specimens (No 1 to No 4) liquid biopsy, solid tumor tissue by bronchoscopic techniques, cytologic material by TBNA combination of methods (tissue biopsy, TBNA and liquid biopsy) and single techniques naïve and processed tumor tissue specimen (eg. microdissection) To assess differences in side effects e.g. periinterventional bleeding | recruiting period approximately 24 months |