Lung Cancer Organoids and Patient Derived Tumor Xenografts (Lung organoids)

Extra tissue will be taken from patient during a procedure in standard of care. Also, through an existing line, 10ml of extra blood will be drawn. From this material the investigator will try to establish matched normal and primary human lung cancer organoids.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Other: Tissue and blood

Detailed Description

Lung (tumor) material obtained from biopsies or surgical resection material that is not needed by the pathologist for diagnosis (i.e. to stage the patient or to perform molecular diagnosis) will be collected and used for the generation of matched normal and lung cancer organoids and/or PDX.

Biopsy material: Patients with (suspected) lung cancer will undergo a bronchoscopy or endobronchial ultrasound guided transbronchial needle aspiration (EBUS/EUS-TBNA) bronchoscopy for the collection of a lung / lymph node biopsy. Biopsies are collected according to standard of care procedures for i.e. the initial diagnosis and staging of lung cancer, and molecular profiling of recurrent tumors. During the standard of care biopsy procedure, an extra biopsy (lung and/or lymph node) will be collected and used for the generation of lung (cancer) organoids:

• Bronchoscopy: biopsy-derived lung (tumor) tissue from endobronchial tumors
• EBUS/EUS-TBNA bronchoscopy: cytology-derived lung (tumor) cells from mediastinal lymph nodes

A 10 ml blood sample will only be collected at the moment blood must be drawn according to standard of care procedures or when the patient has received an intravenous drip. The patient therefore does not require to undergo additional procedures.

Resection material: Patients who are selected to undergo surgical removal of a primary lung cancer will be included. The (tumor) material that will be used to make organoids and PDX will be derived from remaining healthy and tumor tissue that is not needed for the pathologist to make a diagnosis, to stage the patient or to perform a molecular diagnosis. The patient therefore does not require to undergo additional treatments or procedures. A 10 ml blood sample will be collected at the moment blood must be drawn pre-operatively according to standard of care procedures or from the intravenous drip the patient will receive before start surgery. The patient therefore does not require to undergo additional procedures.

Collection of clinical data: Clinical data will be collected from existing standard of care data:

• Histology
• Date diagnosis lung cancer
• TNM classification (eight edition)
• If performed, molecular analysis data such as Epidermal Growth Factor Receptor (EGFR) mutation, Anaplastic Lymphoma Kinase (ALK) translocation, Kirsten Rat Sarcoma (KRAS) viral oncogene homolog mutation etc. (Type of test, results)
• PD-L1 status if available. If available, type of test and PD-L1%
• Type, dose, and date of treatment the patient received before and/or after the collection tumor biopsy (chemotherapy, radiotherapy, tyrosine kinase inhibitors, immunotherapy). If applicable, also the date and dose of all cycles.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Chantal Overhof, BEc.; Phone Number: +31 88 44 55 863; Email: chantal.overhof@maastro.nl
• Study Contact Backup: Name: Ann Claessens; Phone Number: +31 88 44 55 863; Email: ann.claessens@maastro.nl

Study Locations

• Netherlands
  • Heerlen, Netherlands, 6419 PC
    • Recruiting
    • Zuyderland Medical Center
    • Contact: Juliette Degens, MD, PhD; Phone Number: +31 884597810; Email: juliette.degens@zuyderland.nl
    • Principal Investigator: Juliette Degens, MD, PhD
  • Maastricht, Netherlands, 6229 ET
    • Not yet recruiting
    • Maastricht Radiation Oncology (Maastro)
    • Contact: Chantal Overhof, BEc.; Phone Number: +31 884455863; Email: chantal.overhof@maastro.nl
    • Contact: Ann Claessens; Phone Number: +31 884455863; Email: ann.claessens@maastro.nl
    • Principal Investigator: Dirk De Ruysscher, MD, PhD
  • Maastricht, Netherlands, 6229 HX
    • Recruiting
    • MUMC+
    • Contact: Roy Sprooten, MD; Phone Number: +31 43 3871318; Email: r.sprooten@mumc.nl
    • Principal Investigator: Roy Sprooten, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with lung cancer

Description

Inclusion Criteria:

• All patients selected to undergo primary surgical resection of a primary lung cancer. All types of resection are eligible, e.g. wedge resection, segmental resection, lobectomy, pneumonectomy.
• All patients with (suspected) lung cancer that will undergo a bronchoscopy or endobronchial ultrasound guided transbronchial needle aspiration (EBUS/EUS-TBNA) bronchoscopy.

Exclusion Criteria:

There are no exclusion criteria

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
All patiens; There is only one arm in this trial	Other: Tissue and blood; Tissue and blood will be derived from patient during a standard of care procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung cancer organoids	Establishing matched normal and primary human lung cancer organoids from patient-derived (tumor) tissue material by establishing long term culturing and bio-banking conditions for matched normal and primary lung cancer organoids from patient-derived lung (tumor) material. From these, we will In the established organoids we will: • the rate of proliferation and cell death (turnover) will be calculated	1 year
Lung cancer organoids	Establishing matched normal and primary human lung cancer organoids from patient-derived (tumor) tissue material by establishing long term culturing and bio-banking conditions for matched normal and primary lung cancer organoids from patient-derived lung (tumor) material. From these, we will In the established organoids we will: • the size distribution of the organoids	1 year
Lung cancer organoids	Establishing matched normal and primary human lung cancer organoids from patient-derived (tumor) tissue material by establishing long term culturing and bio-banking conditions for matched normal and primary lung cancer organoids from patient-derived lung (tumor) material. From these, we will In the established organoids we will: • determine the frequency of primary, secondary and tertiary organoid formation	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oncogenetic drivers	To define oncogenic drivers in lung cancer organoids	1 year
Tumor heterogeneity	To investigate the stability of (epi-) genetic and phenotypic tumor heterogeneity of cultured organoids compared to a primary/secondary biopsy	1 year
Molecular biology	To predict sensitivity and to get insight in the molecular biology of the response to immunotherapy, radiotherapy, cytotoxic and targeted agents	1 year
Treatment response	To compare treatment response in normal lung organoids and lung cancer organoids	1 year
Xenografts	To establish and characterize patient-derived tumor xenografts	1 year
Therapeutic approaches	To test novel therapeutic approaches in lung cancer organoids and clinically relevant PDX models, including radiotherapy combined with hypoxia activated prodrugs and immunotherapies	1 year
Developing biomarkers	To develop biomarker(s) of tumor response to be able to select patients who will benefit from novel treatment strategies.	1 year
Analysing blood	To analyze (ct)DNA in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year
Analysing blood	To analyze metabolites in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year
Analysing blood	To analyze RNA in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year
Analysing blood	To analyze proteins in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year
Analysing blood	To analyze microvesicles secreted by lung cancer cells in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

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; Lung Neoplasms
• Other Study ID Numbers: Lung Organoids

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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