Lung Cancer Organoids and Patient Derived Tumor Xenografts

Lung Cancer Clinical Trial

— Lung organoids  

Official title:

Lung Cancer Organoids and Patient Derived Tumor Xenografts

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05092009
• Other study ID #: Lung Organoids
• Status: Recruiting
• Start date: October 5, 2022
• Est. completion date: April 1, 2025

Study information

• Verified date: August 2023
• Source: Maastricht Radiation Oncology
• Contact: Chantal Overhof, BEc.
• Phone: +31 88 44 55 863
• Email: chantal.overhof[@]maastro.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: April 1, 2025
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Other:
• Tissue and blood
Tissue and blood will be derived from patient during a standard of care procedure

Locations

Country	Name	City	State
Netherlands	Zuyderland Medical Center	Heerlen
Netherlands	Maastricht Radiation Oncology (Maastro)	Maastricht
Netherlands	MUMC+	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht Radiation Oncology

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Oncogenetic drivers	To define oncogenic drivers in lung cancer organoids	1 year
Secondary	Tumor heterogeneity	To investigate the stability of (epi-) genetic and phenotypic tumor heterogeneity of cultured organoids compared to a primary/secondary biopsy	1 year
Secondary	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
Secondary	Treatment response	To compare treatment response in normal lung organoids and lung cancer organoids	1 year
Secondary	Xenografts	To establish and characterize patient-derived tumor xenografts	1 year
Secondary	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
Secondary	Developing biomarkers	To develop biomarker(s) of tumor response to be able to select patients who will benefit from novel treatment strategies.	1 year
Secondary	Analysing blood	To analyze (ct)DNA in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year
Secondary	Analysing blood	To analyze metabolites in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year
Secondary	Analysing blood	To analyze RNA in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year
Secondary	Analysing blood	To analyze proteins in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year
Secondary	Analysing blood	To analyze microvesicles secreted by lung cancer cells in organoid-derived culture supernatants and corresponding patient-derived blood samples	1 year