Clinical protocol: Feasibility of evaluating abemaciclib neuropharmacokinetics of diffuse midline glioma using intratumoral microdialysis

Edjah K. Nduom, John Glod, Desmond A. Brown, Margaret Fagan, Mahalia Dalmage, John Heiss, Seth M. Steinberg, Cody Peer, William D. Figg, Sadhana Jackson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment responsivity. This is a non-randomized, single-center, phase 1 clinical trial. Up to seven young adult (18–39 years) patients with recurrent high-grade or diffuse midline glioma will be enrolled with the goal of 5 patients completing the trial over an anticipated 24 months. All patients will take abemaciclib pre-operatively for 4.5 days at twice daily dosing. Patients will undergo resection or biopsy, placement of a microdialysis catheter, and 48 hours of dialysate sampling coupled with timed plasma collections. If intratumoral tumor or brain dialysate sampling concentrations are >10nmol/L, or tumor tissue studies demonstrate CDK inhibition, then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy and discontinued with evidence of radiologic or clinical disease progression. The poor survival associated with diffuse midline gliomas underscore the need for improved means to evaluate efficacy of drug delivery to tumor and peritumoral tissue. The findings of this novel study, will provide real-time measurements of BBB function which have the potential to influence future prognostic and diagnostic decisions in such a lethal disease with limited treatment options.

Original languageEnglish
Article numbere0291068
JournalPLoS ONE
Volume18
Issue number9 September
DOIs
StatePublished - Sep 2023
Externally publishedYes

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