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.
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.
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.
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.
Single group
QPOP category 1
Drugcombination regimens with published data in the setting of gliomas
QPOP category 2
Drugcombination 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
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.
Radiological response at follow up MRI
The determination of radiographic response is as per the Response Assessment in Neuro-Oncology (RANO) criteria.
Twelve-month overall survival (OS12)
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.
Number of participant with treatment related haematological and non-haematological toxicities
As defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Click on the lead sponsor to view all of their trials.
National University Hospital, Singapore
Lead sponsor
National University of Singapore
Collaborator
