A phase I dose-escalation trial of GliaSite brachytherapy for recurrent glioblastoma multiforme

Abstract

1548 Background: NABTT opened trial 2106 to determine the maximum tolerated dose (MTD) of GliaSite Brachytherapy (GSBT) in the treatment of recurrent GBM. This trial closed 2004 without reaching the MTD. Methods: Patients with recurrent resectable GBM were enrolled in cohorts of 5 to receive postoperative brachytherapy. A DLT was defined as CTC 2.0 grade 3/4 toxicity not resolved within 1 month of onset or 3 months from end of brachytherapy (whichever was longer), any Grade 5 toxicity, or radiation necrosis requiring craniotomy within 3 months from completion of brachytherapy. Progressive disease (PD) was defined as progressive neurologic abnormalities not explained by causes unrelated to tumor progression; greater than 25% increase in the volume of enhancing tumor; or new enhancement on MRI scan. Results: 12 patients were screened. 7 did not receive GSBT. Of the remaining 5, 1 was taken off study prior to the evaluation endpoint to start new therapy.The median patient age was 56 years (43–67). The median KPS was 90 (60–100). 3 patients had a diagnosis of GBM (WHO IV), 1 had AA (WHO III) and 1 had AO (WHO III). The median number of cycles of previous chemotherapy was 3 (1–6). The median previous external beam radiation therapy dose was 60 Gy (56–63). The median balloon size was 3.0 cm (2.0–4.0). All patients received a dose of 80 Gy @ 1 cm. The median dwell time 116 hrs (115–168). The median delivered radioactivity was 429 mCi (237–661). No DLT was encountered. At the endpoint, 2 had SD, and 2 had PD. The patient taken off study to start a new treatment had a PR. 2 patients were alive at last follow up. The median time of survival will be presented as the data mature. Conclusions: At this time, it was determined that this trial could not complete accrual. Analysis of the early PD suggested that some of the radiographic findings may have represented a reaction to treatment. It was thus decided that the trial would be closed and replaced by a Phase II trial using a fixed dose of GSBT with an endpoint designed to characterize the imaging changes associated with GSBT and correlate these with biologic and pathologic findings at the time of imaging progression. No significant financial relationships to disclose.