Phase II Glioblastoma Multiforme Trial With Central Neuroradiology Review

Challenge

A Phase II trial evaluated a novel treatment for glioblastoma multiforme, the most common and aggressive primary brain tumor in adults. Response assessment in glioblastoma is complicated by pseudoprogression after chemoradiation, by the effect of corticosteroids on enhancement, and by variability in MRI acquisition across sites, all of which can produce apparent progression that is not tumor growth.

The sponsor needed a standardized MRI protocol, blinded neuroradiology review under RANO criteria, and a process that integrated clinical information such as steroid dose into the assessment while preserving blinding to treatment, so that progression-free survival would be measured consistently.

Intrinsic Imaging’s Solution

Intrinsic Imaging developed the protocol imaging section and charter with a standardized brain tumor MRI protocol, qualified sites against it and trained site staff on timepoint scheduling and submission of the clinical data elements RANO requires. Image transfer, blinding and processing were centralized with quality control at receipt.

Board-certified, fellowship-trained neuroradiologists performed blinded independent reads under RANO criteria, with the charter governing measurable disease definition, handling of enhancing and non-enhancing components, the pseudoprogression window and confirmation requirements. Discordant response assessments were adjudicated.

Reader calibration used reference cases spanning true progression, pseudoprogression and treatment effect, and reader agreement was monitored during the trial.

Intrinsic Imaging’s Results

• Approximately 110 patients at 18 sites assessed under blinded RANO double reads with adjudication
• Standardized brain tumor MRI protocol adopted at all sites with unevaluable timepoints under 3%
• Suspected pseudoprogression managed under a documented confirmation workflow, with rationale recorded for every progression determination
• Corticosteroid and clinical data integrated into RANO assessment without compromising reader blinding to treatment arm