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

NCT05532397 | Recruiting

• 1 other identifier: QP/25/05/21
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Glioma, Astrocytic

Keywords

QPOP; patient-derived organoids (PDOs); TMZ/RT resistance

Outcome Measures

Primary Outcomes (1)

• Six-month progression-free survival (PFS 6)

  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 Outcomes (3)

• Radiological response at follow up MRI

  Up to 6 months

• Twelve-month overall survival (OS12)

  Up to 12 months

• Number of participant with treatment related haematological and non-haematological toxicities

  Up to 6 months

Study Arms (1)

QPOP-guided chemotherapy

EXPERIMENTAL

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; Drug: QPOP category 2

Interventions

QPOP category 1 DRUG

combination regimens with published data in the setting of gliomas

QPOP-guided chemotherapy

QPOP category 2 DRUG

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

QPOP-guided chemotherapy

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pre-screening:
• 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.
• 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:
• 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.
• Documented tumor progression based on standard clinical, radiological or histological criteria, and deemed suitable for second line systemic therapy.
• Sufficient tumor tissue available for PDO generation at baseline and at least one available or pending QPOP result.
• Adequate organ function as defined by:
• \. 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.

You may not qualify if:

• Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 2 weeks of study entry.
• 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.
• 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.
• Patients with leptomeningeal dissemination of disease and/or pure spinal high grade gliomas will be excluded.
• Kidney disease which would clinically disqualify the subject from serial MRI scans with gadolinium contrast.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• National University of Singapore: collaborator

Study Sites (2)

Department of Hematology-Oncology, National University Hospital

Singapore, 119074, Singapore

RECRUITING

Ng Teng Fong General Hospital

Singapore, 609606, Singapore

NOT YET RECRUITING

Related Publications (15)

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  PMID: 39058662 DERIVED

MeSH Terms

Conditions

Astrocytoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Andrea Wong

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Wong

CONTACT

+65 6908 2222; andrea_la_wong@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an interventional, non-randomized, open-label study. Enrolled subjects will receive QPOP-guided chemotherapy at the time of first high grade astrocytic glioma recurrence.

Study Record Dates

• First Submitted: September 4, 2022
• First Posted: September 8, 2022
• Study Start: February 17, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 23, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)