Clinical trial NCT04865315: A Living Tissue Bank of Patient-Derived Organoids From Glioma Tumors
Official title: HiLoGlio Organoid Study: 'A Living Tissue Bank of Patient-Derived Organoids From Glioma Tumors'
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Low-grade Glioma
High Grade Glioma
Keywords: Prospective study
Patient-derived organoids
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: Maastricht University Medical Center
name: Zuyderland Medisch Centrum
name: Ziekenhuis Oost-Limburg
First posted: 2021-04-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who have an MRI lesion suspected for a low- or high grade glioma (newly diagnosed or recurrent), who are eligible for a resection of the tumor.

Brief summary: There is a high medical need to improve treatment outcome for high-grade and low-grade glioma since no curative treatment is available. To achieve this goal, a broader understanding is needed of the causes of inter-and intratumoral heterogeneity; glioma dedifferentiation and invasion; the major determinants of malignancy and treatment failure in glioma patients. Patient-derived organoid (PDOs) of high-grade gliomas and low-grade gliomas will be used to identify the mechanisms that underlie this malignant behaviour and treatment resistance. This insight may be used to develop patient avatars to simultaneously test multiple new treatment modalities that are predictive for survival and quality of life of glioma patients.

Detailed description: To establish primary patient-derived three-dimensional organoid cultures from low grade and high-grade gliomas to study the mechanisms that contribute to i.e.

resistance to radiotherapy and/or chemotherapy and immunotherapy, dedifferentiation, tumor invasion among others, in primary and recurrent tumors.

Primary Objectives:

1. Establishment of primary patient-derived organoids (PDO) of 'de novo' and recurrent high-grade glioma (HGG) and low-grade glioma (LGG)
2. Phenotypic, genetic, epigenetic and transcriptomic characterization of HGG and LGG organoids and resemblance to the parental tumor (i.e. characterization of specific cell populations and genomic and transcriptomic profiles of PDOs)
3. Investigation of combinations of new or standard glioma systemic treatments (i.e immunotherapy, chemotherapy) with or without radiation (i.e. protons, photons).

Secondary objectives

1. Establishment of co-cultures of HGG and LGG organoids with immune cells.
2. Investigation of radiation-triggered cell death mechanisms on PDOs after irradiation with photons and protons.
3. Investigation of dedifferentiation mechanisms of LGG to HGG in the context of radiation w/wo immunotherapy.

Eligibility criteria: Inclusion Criteria:

* MRI diagnosis of low grade glioma (LGG) or high grade glioma (HGG)
* Age 18 years or older
* Patient is eligible for a resection of the tumor

Exclusion Criteria:

* Contra-inidication for neurosurgical resection of the tumor.
* Incapacitated patient, unable to give informed consent.

Primary outcomes:
measure: Phenotypic, genetic, epigenetic proteomic and transcriptomic profile of the LGG/HGG PDOs
timeFrame: Baseline tumor resection and blood sampling
Secondary outcomes:
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht Radiation Oncology
state: Limburg
Study officials:
affiliation: Maastro Radiaton Oncology clinic
name: Marc Vooijs, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: