AT-54 * THERMOTHERAPY WITH COATED IRON OXIDE NANOPARTICLES RADIOTHERAPY VERSUS RADIOTHERAPY ALONE IN RECURRENT GLIOBLASTOMA: AN OPEN-LABEL RANDOMIZED CONTROLLED STUDY

Abstract

INTRODUCTION: Limited therapeutic options are available for glioblastoma, the most frequent and malignant brain tumor, after failure of first-line therapy. Therefore, corresponding new antitumor therapies are urgently needed. Hyperthermia and thermoablation kill, disable or sensitize tumor cells to concurrent anticancer treatment depending on duration and temperature, and possibly inhibit the cell's repair system. This clinical safety and efficacy study investigates thermotherapy after stereotactic injection of biocompatible aminosilane-coated superparamagnetic iron oxide nanoparticles into the tumor. These particles, which agglomerate immediately after injection, are stimulated by an external alternating magnetic field, thus generating heat within the tumor while sparing the surrounding healthy tissue. Feasibility, safety, and first efficacy results in combination with radiotherapy have been shown previously. METHODS: NanoTherm monotherapy is evaluated in a run-in phase (24 subjects) and, if effective, in the main study versus a combination with hypofractionated stereotactic radiotherapy (HFSRT) and HFSRT alone in 285 subjects in recurrent glioblastoma. Major eligibility criteria are radiographically and histologically confirmed first progression of supratentorial glioblastoma, a maximum tumor volume of 25 ml, standard radiochemotherapy or radiotherapy alone, at least 6 months off RT, no proximate metallic material, and no previous and concurrent antiangiogenics. After stereotactic deposition of nanoparticle depots in the tumor, six 1-hourly alternating magnetic field sessions are applied twice weekly within 2 h after HFSRT, which is applied as 2.66 Gy fractions (40 Gy in total) 5 days a week for 3 weeks. Patients are followed-up every 3 months for survival, the primary study endpoint. Study accrual began in January 2014.