Perioperative clinical trials for glioma: raising the bar
Journal Title
Journal of Clinical Neuroscience
Abstract
Gliomas are a heterogeneous group of primary brain cancers with poor survival despite multimodality therapy that includes surgery, radiation and chemotherapy. Numerous clinical trials have investigated systemic therapies in glioma, but have largely been negative. Multiple factors have contributed to the lack of progress including tumour heterogeneity, the tumour micro-environment and presence of the blood-brain barrier, as well as extrinsic factors relating to trial design, such as the lack of a contemporaneous biopsy at the time of treatment. A number of strategies have been proposed to progress new agents into the clinic. Here, we review the progress of perioperative, including phase 0 and 'window of opportunity', studies and provide recommendations for trial design in the development of new agents for glioma. The incorporation of pre- and post-treatment biopsies in glioma early phase trials will provide valuable pharmacokinetic and pharmacodynamic data and also determine the target or biomarker effect, which will guide further development of new agents. Perioperative 'window of opportunity' studies must use drugs with a recommended-phase-2-dose, known safety profile and adequate blood-brain barrier penetration. Drugs shown to have on-target effects in perioperative trials can then be evaluated further in a larger cohort of patients in an adaptive trial to increase the efficiency of drug development.
Publisher
Elsevier
Keywords
Clinical trial; Drug resistance; Glioma; Perioperative trials; Phase 0 trial;
WEHI Research Division(s)
Cancer Biology And Stem Cells
PubMed ID
34119258
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2021-06-21 10:26:03
Last Modified: 2021-06-21 10:46:27
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