Prospective Primary Human Lungcancer Organoids to Predict Treatment Response

NCT04859166 | Completed

• 1 other identifier: Organoids lung
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

Organoids are generated from tumor biopsies, taken during a standard procedure. and are a collection of organ-specific cell types that are able to self-organize in-vitro in a manner similar to the in-vivo situation (3D). They have the capability to facilitate in-depth analysis of patient's own tumor material at point of diagnosis and during progressive/recurrent disease. There is currently no published protocol to establish long-term lung cancer organoids from lung cancer patients. Such a methodology would enable the prospective identification of 'patient tailored optimal treatments" as well as the derivation of predictive biomarkers for response and relapse. Apart from organoids, xenograft models also still have their merits. To generate PDX, tumor material will be retrieved from surgical specimens, cut in small pieces, transplanted in the recipient immune deficient animals either subcutaneously or implanted directly into the lung. A tumor with the median growth rate will be serially transplanted in vivo for further therapeutic experiments. Dedicated small animal irradiaton in our facility enables precise local irradiation of lung tumors with minimal radiation exposure of the surrounding normal tissues. Integrated cone beam computed tomography imaging system allows longitudinal monitoring of tumor response to novel treatments.

Conditions

Lung Cancer

Keywords

Organoids; Lung; Cancer

Outcome Measures

Primary Outcomes (10)

• Bio-banking

  To establish long term culturing and bio-banking conditions for primary lung cancer organoids.

  5 years

• Frequency of organoid formation

  To determine the frequency of primary, secondary and tertiary organoid formation

  5 years

• Distribution

  The size distribution of the organoids

  5 years

• Proliferation

  The rate of proliferation and cell death (turnover) will be calculated

  5 years

• PDX models of lung cancer

  To establish PDX models of lung cancer by means of passaging and expansion through subcutaneous engraftment in immune deficient animals and create PDX tumor bank for subsequent experiments

  5 years

• Established PDX histologically

  To characterize established PDX histologically and to compare these characteristics with donor tissue

  5 years

• Established PDX genetically

  To characterize established PDX genetically (most frequently occurring driver mutations in lung cancer) and to compare these characteristics with donor tissue

  5 years

• Established PDX biologically

  To characterize established PDX biologically (proliferation, tumor microenvironment, etc.) and to compare these characteristics with donor tissue

  5 years

• Test treatments

  Using PDX models to test novel anti-cancer treatments such as a hypoxia-activated prodrug (HAP) in combination with radiation

  5 years

• Test treatments

  Using PDX models to develop predictive assay of tumor response to HA

  5 years

Secondary Outcomes (2)

• Test hypotheses

  5 years

• Generate cell lines

  5 years

Interventions

Organoids PROCEDURE

A part of the tumor of approximately 1 cm3 will be removed from the primary tumor.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

In a one year period,30 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 will be derived from 'left-over' 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.

You may qualify if:

• \- Undergo primary surgical resection of a primary lung cancer (e.g. wedge resection, segmental resection, lobectomy, pneumonectomy)

You may not qualify if:

• \- Preceding induction treatment (e.g. induction chemotherapy or chemo-radiotherapy)

Sponsors & Collaborators

• Maastricht Radiation Oncology: lead

Study Sites (2)

Zuyderland Medical Center

Heerlen, 6419 PC, Netherlands

Location

Maastro

Maastricht, 6229 ET, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

A part of the tumor of approximately 1 cm3 will be removed from the primary tumor.

MeSH Terms

Conditions

Lung Neoplasms; Neoplasms

Interventions

Microphysiological Systems

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cell Culture Techniques, Three Dimensional; Cell Culture Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Culture Techniques; In Vitro Techniques; Lab-On-A-Chip Devices; Micro-Electrical-Mechanical Systems; Electrical Equipment and Supplies; Equipment and Supplies

Study Officials

• Marc Vooijs, MD, PhD

  Maastro

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2021
• First Posted: April 26, 2021
• Study Start: November 15, 2017
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: March 15, 2023

Record last verified: 2023-03

Locations

NL (2)