NCT06782984

Drug Response Testing and Repurposing Using Glioblastoma Organoid

Patient-derived Organoids As Predictive Models for Drug Response Testing and Repurporsing in Glioblastoma Therapy

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 150 (estimated)
• Sponsor: Chungnam National University Hospital · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

The aim of this observational study, based on a prospectively collected cohort, is to evaluate the prognostic value of patient-derived organoids in predicting responses to conventional and repurposing drugs, including temozolomide, in patients with primary or recurrent glioblastoma. The primary question is whether the patient's response to temozolomide is recapitulated in their corresponding patient-derived glioblastoma organoid (GBO). Patient drug responses are evaluated using survival data, while GBO drug responses are assessed through a drug-response testing platform utilizing cell viability assays. Additionally, this platform is used to explore the potential application of various chemotherapeutic agents.

Detailed description

Glioblastoma multiforme (GBM) remains a highly aggressive brain tumor with limited treatment options and a poor prognosis. Temozolomide (TMZ) is the only approved first-line therapy, but frequent resistance limits its efficacy, highlighting the urgent need for alternative treatments. Patient-derived glioblastoma organoids (GBOs) offer a promising preclinical model for personalized drug testing and therapy development. In our previous study, we established 20 GBO lines using a serum-free protocol, preserving the histopathological and genomic features of the parental tumors. Additionally, GBO Drug Sensitivity Testing (GBO-DST) was developed to evaluate TMZ responsiveness and to screen several FDA-approved drugs, including Lazertinib and Regorafenib. The GBO-DST was successfully validated by correlating IC50 values with progression-free survival, GBO size measurement after treatment, and histopathological evaluation. The goal of this study is to investigate whether a preclinical model using GBOs can eventually replace clinical trials. Therefore, it is necessary to collect diverse genetic information from patients in a multicenter setting, along with corresponding GBOs that recapitulate the patient tumors. Using GBO-DST, external cohort validation will be performed. Concurrently, the study aims to predict the potency of multi-kinase inhibitors or EGFR-TKIs, which are expected to show efficacy based on prior research, and compare these predictions against clinical outcomes. This study aims to establish 100 GBO lines, targeting the enrollment of 150 patients, considering a previous success rate of 66.7% for GBO establishment. Since the study requires tumor tissue and genetic information from patients, IRB approvals from multiple institutions have been secured (including five tertiary hospitals in South Korea: Chungnam National University Hospital, Soonchunhyang University Hospital, Keimyung University Hospital, Yeungnam University Hospital, and Dong-A University Hospital). However, as this study retrospectively correlates patient clinical outcomes with GBO-DST results, it does not involve direct interventions with patients. Specifically, GBO-DST results for multiple candidate drugs will not be used to alter patients' treatment regimens. The study collects clinical information and genetic data from patients, with clinical outcomes defined as progression-free survival and overall survival. Radiologic data will be prospectively collected to achieve these objectives. Through this study, we aim to validate the findings of previous research by confirming that GBO-DST accurately recapitulates patients' drug responses. Furthermore, we seek to establish GBO-DST as a preclinical trial platform capable of replacing traditional clinical trials.

Conditions

• Glioblastoma
• Organoid

Interventions

Type	Name	Description
OTHER	Organoid-based drug sensitivity test	The intervention in this study involves utilizing glioblastoma organoids (GBOs) to perform an organoid-based drug sensitivity test (DST) and retrospectively comparing the results with clinical outcomes. Notably, no interventions will be applied to participants based on GBO-DST results; the study is limited to retrospective analysis. The GBO-DST is conducted by performing a drug response assay with temozolomide to determine the half-maximal inhibitory concentration (IC50), which serves to classify GBOs as TMZ-sensitive or TMZ-resistant. This classification is further validated through GBO cell survival analysis.

Timeline

• Start date: 2021-08-18
• Primary completion: 2028-12-01
• Completion: 2030-12-01
• First posted: 2025-01-20
• Last updated: 2025-01-20

Locations

1 site across 1 country: South Korea