Evaluation of ex vivo drug combination optimization platform in recurrent high grade astrocytic glioma: An interventional, non-randomized, open-label trial protocol.

Autor: Toh TB; The N.1 Institute for Health (N.1), National University of Singapore, Singapore, Singapore.; The Institute for Digital Medicine (WisDM), National University of Singapore, Singapore, Singapore., Thng DKH; The N.1 Institute for Health (N.1), National University of Singapore, Singapore, Singapore.; Cancer Science Institute of Singapore (CSI), National University of Singapore, Singapore, Singapore., Bolem N; Division of Neurosurgery, Department of Surgery, National University Hospital, Singapore, Singapore., Vellayappan BA; Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore., Tan BWQ; Cancer Science Institute of Singapore (CSI), National University of Singapore, Singapore, Singapore., Shen Y; The N.1 Institute for Health (N.1), National University of Singapore, Singapore, Singapore.; Cancer Science Institute of Singapore (CSI), National University of Singapore, Singapore, Singapore., Soon SY; Department of Haematology-Oncology, National University Hospital, Singapore, Singapore., Ang YLE; Department of Haematology-Oncology, National University Hospital, Singapore, Singapore., Dinesh N; Division of Neurosurgery, Department of Surgery, National University Hospital, Singapore, Singapore., Teo K; Division of Neurosurgery, Department of Surgery, National University Hospital, Singapore, Singapore., Nga VDW; Division of Neurosurgery, Department of Surgery, National University Hospital, Singapore, Singapore., Low SW; Division of Neurological Surgery, Ng Teng Fong General Hospital, Singapore, Singapore., Khong PL; Department of Diagnostic Imaging, National University Hospital, Singapore, Singapore.; Clinical Imaging Research Centre (CIRC), National University of Singapore, Singapore, Singapore., Chow EK; The N.1 Institute for Health (N.1), National University of Singapore, Singapore, Singapore.; The Institute for Digital Medicine (WisDM), National University of Singapore, Singapore, Singapore.; Cancer Science Institute of Singapore (CSI), National University of Singapore, Singapore, Singapore., Ho D; The N.1 Institute for Health (N.1), National University of Singapore, Singapore, Singapore.; The Institute for Digital Medicine (WisDM), National University of Singapore, Singapore, Singapore., Yeo TT; Division of Neurosurgery, Department of Surgery, National University Hospital, Singapore, Singapore., Wong ALA; Cancer Science Institute of Singapore (CSI), National University of Singapore, Singapore, Singapore.; Department of Haematology-Oncology, National University Hospital, Singapore, Singapore.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jul 26; Vol. 19 (7), pp. e0307818. Date of Electronic Publication: 2024 Jul 26 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0307818
Abstrakt: Introduction: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients.
Methods: This is an interventional, non-randomized, open-label study, which aims to enroll 10 patients who will receive QPOP-guided chemotherapy at the time of first HGG recurrence following progression on standard first-line therapy. At the initial presentation of HGG, tumor will be harvested for primary PDO generation during the first biopsy/surgery. At the point of tumor recurrence, patients will be enrolled onto the main study to receive systemic therapy as second-line treatment. Subjects who undergo surgery at the time of recurrence will have a second harvest of tissue for PDO generation. Established PDOs will be subject to QPOP analyses to determine their therapeutic sensitivities to specific panels of drugs. A QPOP-guided treatment selection algorithm will then be used to select the most appropriate drug combination. The primary endpoint of the study is six-month progression-free survival. The secondary endpoints include twelve-month overall survival, RANO criteria and toxicities. In our radiological biomarker sub-study, we plan to evaluate novel radiopharmaceutical-based neuroimaging in determining blood-brain barrier permeability and to assess in vivo drug effects on tumor vasculature over time.
Trial Registration: This trial was registered on 8th September 2022 with ClinicalTrials.gov Identifier: NCT05532397.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: EKHC and DH are shareholders in KYAN Technologies. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2024 Toh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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