The phase 3 Gliofocus trial (NCT06388733) is underway to assess the efficacy of niraparib (Zejula) compared to temozolomide (Temodar) in patients with newly diagnosed MGMT unmethylated glioblastoma. This international trial, sponsored by the Ivy Brain Tumor Center, seeks to improve survival rates and quality of life for this challenging patient population.
Rationale Behind Niraparib
The Gliofocus trial builds on findings from a proof-of-concept hybrid study (NCT05076513) presented at the 2024 ASCO Annual Meeting. The earlier study demonstrated a median overall survival (OS) of 20.3 months among patients treated with niraparib in combination with radiotherapy. Notably, niraparib achieved high drug concentrations in Gadolinium-nonenhancing newly diagnosed glioblastoma tissue, surpassing other PARP inhibitors evaluated. No new safety signals were identified when niraparib was combined with radiotherapy.
Clinical Significance and Trial Objectives
Nader Sanai, MD, director of the Ivy Brain Tumor Center, emphasized the need for clinically meaningful improvements in glioblastoma treatment. "What we’re looking to do with this trial is set a benchmark that’s clinically relevant for patients and providers. The [OS] target for the study is 18 months, which is to effectively convert [a] 12-month natural history to a natural history closer to the methylated glioblastoma population," Sanai explained. He added that this improvement could significantly benefit patients, providers, and caregivers, potentially enhancing quality of life.
Expediting Clinical Trials
Traditionally, phase 3 clinical trials can take many years to progress. Yoshie Umemura, MD, chief medical officer of the Ivy Brain Tumor Center, highlighted the center's unique platform for accelerating clinical trial development. By streamlining processes and fostering multidisciplinary collaboration, the center aims to bring new treatments to patients more quickly. "We were able to move it just in a few years from phase zero and phase 2 to a phase 3 international trial," Umemura noted. This expedited approach is crucial for addressing the urgent need for effective glioblastoma therapies.
Trial Design and Patient Population
The Gliofocus trial compares niraparib with temozolomide in adult participants with newly diagnosed, MGMT unmethylated glioblastoma. The primary endpoint is overall survival, with secondary endpoints including quality of life and progression-free survival. By targeting an OS of 18 months, the trial seeks to transform the natural history of this aggressive cancer and provide a clinically relevant benefit for patients.
