Influence of Biopsy Technique on Moleculargenetic Tumor Characterisation in NSCLC (PROFILER)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung; Pathology, Molecular
• Intervention / Treatment: Procedure: Forceps biopsy; Procedure: Cryobiopsy

• Study Type: Interventional
• Enrollment (Anticipated): 540
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maik Haentschel, MD; Phone Number: 82711 +49707129; Email: maik.Haentschel@med.uni-tuebingen.de
• Study Contact Backup: Name: Juergen Hetzel, MD; Phone Number: 82711 +49707129; Email: juergen.hetzel@med.uni-tuebingen.de

Study Locations

• Germany
  • Tuebingen, Germany, 72076
    • Recruiting
    • University of Tuebingen
    • Contact: Maik Haentschel, MD; Phone Number: 82711 +49707129; Email: maik.Haentschel@med.uni-tuebingen.de
    • Contact: Juergen Hetzel, MD; Phone Number: 82711 +49707129; Email: juergen.hetzel@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of informed consent to the study and the study specific procedures prior to any study intervention
2. Male or female patients aged ≥18 years
3. Patients with primary diagnosis of suspected lung cancer OR Patients with known NSCLC and suspected relapse after therapy
4. Bronchoscopically visible tumor

Exclusion Criteria:

1. Preexisting malignancy other than NSCLC

2. 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
3. Previous enrolment in the present study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Forceps group	Procedure: Forceps biopsy; Endobronchial biopsy with the forceps
Experimental: Cryobiopsy group	Procedure: Cryobiopsy; Endobronchial biopsy with the cryobiopsy probe

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qualitative tumor DNA determination using next generation sequencing techniques for the different specimens	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	recruiting period approximately 24 months
Quantitative tumor DNA determination using next generation sequencing techniques for the different specimens	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	recruiting period approximately 24 months

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2018
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: March 11, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: PROFILER study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No