Drug Response Testing and Repurposing Using Glioblastoma Organoid

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

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Organoid
• Intervention / Treatment: Other: Organoid-based drug sensitivity test

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.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Kyung Hwan Kim, MD, PhD; Phone Number: 82-42-280-7367; Email: nskhkim@cnuh.co.kr

Study Locations

• Korea, Republic of
  • Chungnam
    • Daejeon, Chungnam, Korea, Republic of, 35015
      • Recruiting
      • Chungnam National University Hospital
      • Contact: Kyung Hwan Kim, MD, PhD; Phone Number: 82-42-280-7367; Email: nskhkim@cnuh.co.kr
      • Contact: Kyung Hwan Kim, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

patients diagnosed with primary or recurrent glioblastoma

Description

Inclusion Criteria:

• primary or recurrent glioblastoma
• patients treated with standard treatment including surgery and temozolomide based chemoradiation therapy
• sufficient tumor sample is available for organoid culture

Exclusion Criteria:

• patients who are not underwent concurrent chemoradiation therapy (CCRT) following surgery
• failed to obtain MRI scan after CCRT
• patients refusal

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

glioblastoma; prospectively enrolled

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	Radiologic progression time following the RANO 2.0 criteria	12 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	patient survival time	18 months after surgery

Collaborators and Investigators

• Sponsor: Chungnam National University Hospital
• Collaborators: Yeungnam University Hospital; Keimyung University Dongsan Medical Center; Soonchunhyang University Hospital; Dong-A University Hospital; Korea Advanced Institute of Science and Technology
• Investigators: Principal Investigator: Kyung Hwan Kim, MD, PhD, Department of Neurosurgery, Chungnam National University Hospital; Principal Investigator: Kijoon Yoon, PhD, Korea Advanced Institute of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2021
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: glioblastoma; organoid; GBO; drug-screening
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: CNUH 2021-08-020-012

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
• product manufactured in and exported from the U.S.: No