Evaluation of ex Vivo Drug Combination Optimization Platform in Recurrent High Grade Astrocytic Glioma

September 21, 2025 updated by: National University Hospital, Singapore
This is an interventional, non-randomized, single site study. Brain tumor samples will be collected from patients for organoids generation and subject to panel drugs screening and QPOP analysis to derive the optimal drug combinations for treatment at the time of first high grade astrocytic glioma recurrence. The investigators hypothesize that patient-derived organoids (PDOs) mimic the biological characteristics of high grade astrocytic gliomas and serve as an ideal platform for the evaluation of drug sensitivities, accurately reflecting the patient's therapeutic response to the drugs.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aims to test the feasibility of Quadratic Phenotypic Optimization Platform (QPOP) application in high grade astrocytic glioma, by first establishing clinically relevant high grade astrocytic glioma organoid models, followed by the utility of QPOP-derived drug combinations in high grade astrocytic glioma.

The primary purpose of this study is not hypothesis testing, but to assess the feasibility of QPOP-guided therapy for recurrent high grade astrocytic glioma to be used in a larger scale study. Therefore, this study does not have a formal sample size, but rather, a set benchmarks to determine feasibility.

Specific Aim 1: To establish primary and corresponding temozolomide/radiotherapy (TMZ/RT)-resistant high grade astrocytic glioma patient-derived organoids.

Specific Aim 2: To determine the utility of QPOP (Quadratic Phenotypic Optimization Platform)-derived drug combinations in treating recurrent high grade astrocytic glioma.

Specific Aim 3: To evaluate the use of non-invasive imaging tools (Ga68-NEB PET/MRI and DCE-MRI) to track BBB permeability over time in high grade astrocytic glioma patients, and correlate this with pathological biomarkers, therapeutic response determined by follow up standard MRI and clinical outcomes.

Male and female subjects aged 21 years and above with suspected high grade astrocytic glioma planned for surgery/ biopsy followed by adjuvant chemoradiotherapy will be invited to participate in the pre-screening study. Subjects will only be enrolled in the main study if they had pathologically confirmed high grade astrocytic glioma, and received adjuvant treatment comprising standard-of-care therapy with surgery/biopsy followed by temozolomide and radiotherapy.

Pre-screening phase:

In pre-screening phase, patients will be approached for pre-screening consent at the time of first suspected diagnosis of a high grade astrocytic glioma and tumor will be harvested at the time of initial surgery/ biopsy for the generation of PDOs. Once the histological diagnosis of high grade astrocytic glioma is confirmed and the patient is planned for adjuvant temozolomide and radiotherapy, they will undergo baseline standard MRI plus Ga68-NEB PET/MRI and DCE-MRI imaging within one week of the planned radiotherapy simulation date. Patients will then undergo standard-of-care treatment for high grade astrocytic glioma with adjuvant concurrent temozolomide and radiotherapy (TMZ/RT)1, and will be evaluated by the primary oncologist routinely with clinical examination, laboratory tests and regular neuro-imaging. High grade astrocytic glioma organoids will be generated from resected tumour samples and QPOP analyses will be performed to identify specific drug combinations to guide clinical management at the time of first relapse.

Main study:

At the time of documented tumor recurrence, eligible patients will be reassessed for suitability to participate in the main study and approached for their informed consent to enter this phase of the study. During the main study, patients will receive QPOP-guided systemic therapy for the treatment of their relapsed high grade glioma and will be assessed regularly for safety and efficacy of this therapy. In addition, patients will undergo standard MRI plus investigational Ga68-NEB PET/MRI and DCE-MRI imaging prior to and 8 weeks (+/- 1 week) after QPOP-guided systemic therapy. Subsequent to this, radiological assessment of their disease will revert to standard clinical protocols with routine standard MRI imaging.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Singapore
      • Singapore, Singapore, 609606
        • Not yet recruiting
        • Ng Teng Fong General Hospital
        • Contact:
          • Shiong Wen Low
          • Phone Number: +65 6908 2222
        • Principal Investigator:
          • Shiong Wen Low
      • Singapore, Singapore, 119074
        • Recruiting
        • Department of Hematology-Oncology, National University Hospital
        • Contact:
        • Principal Investigator:
          • Andrea Wong

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Pre-screening:

  1. Patients 21 years of age or older, with ECOG performance status 0 to 2, and with a life expectancy of more than 3 months with suspected high grade astrocytic glioma, fit for treatment comprising standard-of-care therapy with adjuvant temozolomide and radiotherapy if the diagnosis of high grade astrocytoma is pathologically confirmed.

  2. Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent.

    • Patients will be enrolled at the time of initial surgery but study imaging and further PDO generation will not take place if the patient is subsequently found not to meet the histological criteria or will not be receiving standard adjuvant temozolomide/ radiotherapy.

All subsequent criteria apply to the main study only:

  1. Patients 21 years of age or older, with ECOG performance status 0 to 2, and life expectancy of more than 3 months with pathologically confirmed high grade astrocytic glioma, having undergone first-line standard-of-care therapy with surgery/biopsy followed by temozolomide and radiotherapy. Subjects with truncated adjuvant chemoradiotherapy may be enrolled at the Principal Investigator's discretion.
  2. Documented tumor progression based on standard clinical, radiological or histological criteria, and deemed suitable for second line systemic therapy.
  3. Sufficient tumor tissue available for PDO generation at baseline and at least one available or pending QPOP result.
  4. Adequate organ function as defined by:

1. Bone marrow function i. Haemoglobin ≥ 9g/dl ii. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L iii. Platelet count ≥ 100 x 109/L. 2. Liver function i. Bilirubin < 2.5x upper limit of normal (ULN) ii. Alanine transaminase (ALT) and aspartate transaminase (AST) < 2.5x ULN or < 5x ULN if liver metastases are present iii. Prothrombin time (PT) within the normal range for the institution. 3. Renal function i. Plasma creatinine <1.5x institutional ULN 5) Capable of swallowing tablets. 6) Recovery from any previous drug- or procedure-related toxicity to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 Grade 0 or 1 (except alopecia), or to baseline preceding the prior treatment.

Exclusion Criteria (both pre-screening/ main study)

  1. Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 2 weeks of study entry.
  2. Pregnancy or breastfeeding at the point where systemic anti-cancer therapy is initiated. Women of childbearing potential must have a negative pregnancy test at the point where systemic anti-cancer therapy is initiated. Women of childbearing potential and men, must agree to use adequate contraception (barrier method of birth control) while on anti-cancer treatment and until at least 3 months after the last study drug administration.
  3. Concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours (Ta, Tis & T1) or any cancer curatively treated less than 5 years prior to study entry.
  4. Patients with leptomeningeal dissemination of disease and/or pure spinal high grade gliomas will be excluded.
  5. Kidney disease which would clinically disqualify the subject from serial MRI scans with gadolinium contrast.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: QPOP-guided chemotherapy
Subjects enrolled in the study will be administered combination of chemotherapy derived from QPOP analysis based on in vitro drug screening panels which comprises anti-cancer agents which have previously been evaluated in recurrent high grade astrocytic glioma.
Drug: QPOP category 1
combination regimens with published data in the setting of gliomas
Drug: QPOP category 2
combination regimens where there is published data on intracranial activity and anti-glioma effect of the individual agents either as monotherapy or in combination with other agents, and where there is published safety data on the combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Six-month progression-free survival (PFS 6)
Time Frame: up to 6 months
Defined as the time from the start of study treatment to documented progression of disease or death; PFS6 refers to the percentage of patients who are alive and free of high grade astrocytic glioma progression at 6 months.
up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiological response at follow up MRI
Time Frame: Up to 6 months
The determination of radiographic response is as per the Response Assessment in Neuro-Oncology (RANO) criteria.
Up to 6 months
Twelve-month overall survival (OS12)
Time Frame: Up to 12 months
OS is defined as the length of time from the start of study treatment, that patients diagnosed with the disease are still alive. OS12 refers to the percentage of patients who are alive at 12 months.
Up to 12 months
Number of participant with treatment related haematological and non-haematological toxicities
Time Frame: Up to 6 months
As defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University Hospital, Singapore

Collaborators

National University of Singapore

Investigators

  • Principal Investigator: Andrea Wong, National University Hospital, Singapore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 17, 2023

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

September 4, 2022

First Submitted That Met QC Criteria

September 4, 2022

First Posted (Actual)

September 8, 2022

Study Record Updates

Last Update Posted (Estimated)

September 23, 2025

Last Update Submitted That Met QC Criteria

September 21, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • QP/25/05/21

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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