NABTT 2105: A phase I dose-escalation trial of GliaSite brachytherapy with conventional radiation therapy for newly diagnosed glioblastoma multiforme

Abstract

1570 Background: NABTT opened trial 2105 to determine the maximum tolerated dose (MTD) of GliaSite Brachytherapy (GSBT) with external beam radiation therapy (EBRT) in the treatment of newly-diagnosed GBM (NDGBM). Methods: Patients were enrolled in cohorts of 5 and received postoperative GSBT followed by conventional EBRT to 46 Gy +14 Gy boost. EBRT began within 30 days after GSBT, but not more than 60 days post surgery. 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 GSBT (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; > 25% increase in the volume of enhancing tumor; or new enhancement on MRI. Results: 13 patients were screened. 10 were treated with GSBT of which 8 were replaced: 5 had imaging progression before the evaluation endpoint was reached; 1 died of PE; 1 was taken off study to start new therapy; and 1 received incorrect dose of GSBT. The median patient age was 57 years (27–68); median KPS was 90 (60–100); median balloon size was 3 cm (2–4); median GSBT dose was 70 Gy at 1 cm depth (53–70); median dwell time was 95 hrs (92–165); and median delivered radioactivity was 365 mCi (195–419). No DLT was encountered. 6 patients were alive at last follow up. The median time of survival will be presented as data mature. Conclusions: As a significant number of patients did not reach the evaluation endpoint, it was determined that this trial could not be completed. Analysis of the MRIs suggested that radiographic changes may have represented treatment response and not PD. Phase III EORTC trial data showed that patients with NDGBM should be treated with concomitant temozolomide. It was therefore decided to close the trial and replace it with a Phase II trial using fixed-dose GSBT with temozolomide, the goal being to characterize the associated imaging changes and correlate these with pathologic findings at the time of imaging progression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Proxima Therapeutics Proxima Therapeutics