Abstract CT313: Phase Ib trial of dodecafluoropentane as a radiation sensitizer during chemoradiation for glioblastoma

Abstract

Abstract Purpose: Using post-resected glioblastoma multiforme (GMB) patients to evaluate the pharmacokinetics, safety and potential survival benefit of Dodecafluoropentane emulsion (DDFPe) in combination with the current standard of care; radiation therapy (RT) and temozolomide (TMZ). Glioblastoma multiforme (GBM) is known to be a hypoxic tumor. Tumor hypoxia limits response to RT. DDFPe is an oxygen therapeutic (OT) which transports more than 100x more oxygen as other tested fluorocarbons OT’s. Studies in tumor xenografts show that DDFPe increases tumor pO2 by up to 400% and mitigates radiation resistance. Methods: Previously untreated GBM patients with post-resected residual tumor visible on MRI post surgery were enrolled. Patients received standard RT (60 Gray in 30 fractions over 6 weeks) with concurrent and adjuvant TMZ. In addition, DDFPe was infused intravenously over 30 minutes immediately prior to each fraction of RT while patients simultaneously breathed carbogen (98%O2:2% CO2). DDFPe was dosed using an accelerated titration design with 1 patient per dose level. Blood samples were drawn to evaluate DDFP pharmacokinetics. Objective tumor responses were assessed with gadolinium-enhanced MRI scans and RANO criteria, and tissue oxygen level dependent (TOLD) MRI was employed as an exploratory biomarker of tumor oxygenation. Results: Two patients have been enrolled to date. The first patient received DDFPe at 0.05 cc/kg and completed chemoradiation and 2 cycles of adjuvant TMZ with dose reduction or delay. Therapy was well tolerated except for transient grade 3 ALT elevation during recovery from chemoradiation. A post-radiation MRI scan showed stable disease. The second patient has completed a regimen of chemoradiation in combination with DDFPe at 0.1 cc/kg. Conclusions: DDFPe administration prior to each radiation fraction during standard chemoradiation of GBM is feasible. Further dose escalation od DDFPe is planned to establish a maximum tolerated dose and recommended dose for an envisioned Phase IIb multi-center GBM trial of DDFPe in combination with the accepted standard of care. Citation Format: Jason Lickliter, Jeremy Ruben, Olivia Longacre, David Wilson, Evan Unger. Phase Ib trial of dodecafluoropentane as a radiation sensitizer during chemoradiation for glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT313. doi:10.1158/1538-7445.AM2015-CT313