Data from First-in-Human Phase I Clinical Trial of Pharmacologic Ascorbate Combined with Radiation and Temozolomide for Newly Diagnosed Glioblastoma

• DOI: 10.1158/1078-0432.c.6527853.v1
• Publication Date: 2023-04-01T06:24:40Z
• Authors: Bryan G. Allen; Kellie L. Bodeker; Mark C. Smith; Varun Monga; Sonia Sandhu; Raymond Hohl; Thomas Carlisle; Heather Brown; Nancy Hollenbeck; Sandy Vollstedt; Jeremy D. Greenlee; Matthew A. Howard; Kranti A. Mapuskar; Steven N. Seyedin; Joseph M. Caster; Karra A. Jones; Joseph J. Cullen; Daniel Berg; Brett A. Wagner; Garry R. Buettner; Mindi J. TenNapel; Brian J. Smith; Douglas R. Spitz; John M. Buatti
• Keywords: Temozolomide

<div>AbstractPurpose:<p>Standard treatment for glioblastoma (GBM) includes surgery, radiation therapy (RT), and temozolomide (TMZ), yielding a median overall survival (OS) of approximately 14 months. Preclinical models suggest that pharmacologic ascorbate (P-AscH<sup>−</sup>) enhances RT/TMZ antitumor effect in GBM. We evaluated the safety adding P-AscH<sup>−</sup> to standard therapy.</p>Patients Methods:<p>This first-in-human trial was divided into an RT phase (concurrent RT/TMZ/P-AscH<sup>−</sup>) adjuvant (ADJ) (post RT/TMZ/P-AscH<sup>−</sup> phase). Eight dose cohorts were until targeted plasma levels achieved (≥20 mmol/L). In ADJ phase, doses escalated each subject at cycle concentrations ≥20 mmol/L. infused 3 times weekly during 2 continuing six cycles or disease progression. Adverse events quantified by CTCAE (v4.03).</p>Results:<p>Eleven subjects evaluable. No dose-limiting toxicities occurred. Observed consistent with historical controls. related study drug dry mouth chills. Targeted 20 mmol/L 87.5 g cohort; diminishing returns realized higher cohorts. Median progression-free (PFS) 9.4 months OS 18 undetectable <i>MGMT</i> promoter methylation (<i>n = 8</i>), PFS 10 23 months.</p>Conclusions:<p>P-AscH<sup>−</sup>/RT/TMZ is safe promising clinical outcomes warranting further investigation.</p></div>