IPAX-1: Phase I/II study of 131I-iodo-phenylalanine combined with external radiation therapy as treatment for patients with glioblastoma multiforme.

Abstract

TPS2578 Background: Many tumor types, including glioblastoma multiforme (GBM), overexpress the L-type amino transporter 1 (LAT-1). 131I-iodo-phenylalanine (131I-IPA) is a small-molecule amino acid derivative taken up by LAT-1 with designated orphan status in the United States and European Union for the treatment of GBM. In preclinical research, combining 131I-IPA with external radiation therapy (XRT) yielded additive cytotoxic effects (Israel et al. Nucl Med Biol 2011). Tumor accumulation of 131I-IPA was shown in a proof-of-principle study (Baum et al. Nucl Med Mol Imaging 2011) and confirmed with single dosing of 2–7 GBq 131I-IPA in combination with XRT in patients with recurrent GBM (Verburg et al. Nuklearmedizin 2013). The 131I-IPA + XRT as Treatment for Patients with Glioblastoma Multiforme (IPAX-1) study evaluates the safety, tolerability, dosing schedule, and preliminary efficacy of 131I-IPA in combination with second-line XRT in patients with recurrent GBM. Methods: IPAX-1 is a multi-center, open-label, phase 1/2, dose-finding study recruiting patients with previously confirmed histological diagnosis of GBM and evidence of first recurrence. Other key inclusion criteria are history of GBM standard therapy, at least 6 months since end of first-line XRT, pathologically increased amino acid tumor uptake shown by molecular imaging, and current indication for repeat radiation. Participants receive intravenous 131I-IPA either as a single fraction (1f) followed by XRT, or as three equal fractions (3f) at weekly intervals followed by XRT commencing between the first and second 131I-IPA administration. The 1f regimen (n = 5) evaluates single administration of 2 GBq 131I-IPA. The 3f regimen is used to assess dose escalation, starting with 2 GBq (3 × 0.66 GBq; n = 5) and increasing in 2 GBq increments (n = 3 per activity level). The highest total dose planned is 8 GBq. XRT delivery is in 18 fractions (2 Gy each) on consecutive working days over 4 weeks. The study’s primary aim is to assess the safety and tolerability of 131I-IPA + XRT. Secondary objectives include evaluating the maximum tolerated dose of 131I-IPA, feasibility of fractionated administration, radiation absorbed dose to tumor and biodistribution; and exploring the antineoplastic effect of combination therapy. IPAX-1 enrollments began in July 2019; the study will enroll up to 44 patients and is currently recruiting at five sites in Europe and Australia. Clinical trial information: NCT03849105 .