Dataset Information

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

ABSTRACT:

Purpose

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^-) enhances RT/TMZ antitumor effect in GBM. We evaluated the safety of adding P-AscH^- to standard RT/TMZ therapy.

Patients and methods

This first-in-human trial was divided into an RT phase (concurrent RT/TMZ/P-AscH^-) and an adjuvant (ADJ) phase (post RT/TMZ/P-AscH^- phase). Eight P-AscH^- dose cohorts were evaluated in the RT phase until targeted plasma ascorbate levels were achieved (≥20 mmol/L). In the ADJ phase, P-AscH^- doses were escalated in each subject at each cycle until plasma concentrations were ≥20 mmol/L. P-AscH^- was infused 3 times weekly during the RT phase and 2 times weekly during the ADJ phase continuing for six cycles or until disease progression. Adverse events were quantified by CTCAE (v4.03).

Results

Eleven subjects were evaluable. No dose-limiting toxicities occurred. Observed toxicities were consistent with historical controls. Adverse events related to study drug were dry mouth and chills. Targeted ascorbate plasma levels of 20 mmol/L were achieved in the 87.5 g cohort; diminishing returns were realized in higher dose cohorts. Median progression-free survival (PFS) was 9.4 months and median OS was 18 months. In subjects with undetectable MGMT promoter methylation (n = 8), median PFS was 10 months and median OS was 23 months.

Conclusions

P-AscH^-/RT/TMZ is safe with promising clinical outcomes warranting further investigation.

SUBMITTER: Allen BG

PROVIDER: S-EPMC6858950 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Allen Bryan G BG Bodeker Kellie L KL Smith Mark C MC Monga Varun V Sandhu Sonia S Hohl Raymond R Carlisle Thomas T Brown Heather H Hollenbeck Nancy N Vollstedt Sandy S Greenlee Jeremy D JD Howard Matthew A MA Mapuskar Kranti A KA Seyedin Steven N SN Caster Joseph M JM Jones Karra A KA Cullen Joseph J JJ Berg Daniel D Wagner Brett A BA Buettner Garry R GR TenNapel Mindi J MJ Smith Brian J BJ Spitz Douglas R DR Buatti John M JM

Clinical cancer research : an official journal of the American Association for Cancer Research 20190819 22

<h4>Purpose</h4>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 of adding P-AscH<sup>-</sup> to standard RT/TMZ therapy.<h4>Patients and methods</h4>This first-in-human trial was divided into an RT phase (concurrent RT/TMZ/P-AscH< ...[more]

PMID: 31427282

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Dataset Information

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

Purpose

Patients and methods

Results

Conclusions

Publications

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

Similar Datasets

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