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| Home > Publications database > Phase 0 and Window of Opportunity Clinical Trial Design in Neuro-Oncology: A RANO Review. |
| Home > Publications database > Phase 0 and Window of Opportunity Clinical Trial Design in Neuro-Oncology: A RANO Review. |
| Journal Article | DKFZ-2020-01532 |
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2020
Oxford Univ. Press
Oxford
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Please use a persistent id in citations: doi:10.1093/neuonc/noaa149
Abstract: Glioblastoma is a devastating disease with poor prognosis. Few effective chemotherapeutics are currently available, and much effort has been extended to identify new drugs capable of slowing tumor progression. The phase 0 trial design was developed to facilitate early identification of promising agents for cancer that should undergo accelerated approval. This design features an early in-human study that enrolls a small number of patients that receive sub-therapeutic doses of medication with the goals of describing pharmacokinetics through drug blood level measurements, and by determining intra-tumoral concentrations of the investigational compound as well as pharmacodynamics by studying the biochemical and physiological effects of drugs. In neuro-oncology, however, the presence of the blood-brain barrier and difficulty in obtaining brain tumor tissue warrant a separate set of considerations. In this manuscript, we critically reviewed the protocols used in all brain tumor related in-human phase 0 and phase 0-like ('window of opportunity') studies between 1993 and 2018, as well as ongoing clinical trials, and identified major challenges in trial design as applied to central nervous system tumors that include surgical specimen collection and storage, brain tumor drug level analysis, and confirmation of drug action. We therefore propose that phase 0 trials in neuro-oncology should include 1) only patients in whom a resection of the tumor is planned, 2) use of clinical doses of an investigational agent, 3) tissue sampling from enhancing and non-enhancing portions of the tumor, and 4) assessment of drug-specific target effects. Standardization of clinical protocols for phase 0/window of opportunity studies can help accelerate the development of effective treatments for glioblastoma.
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