Study of Paxalisib Combined With Temozolomide for Adults With High Grade Malignant Brain Tumors Including Glioblastoma

What this Trial Is About

Researchers are evaluating the safety, tolerability, and preliminary antitumor activity of paxalisib combined with temozolomide in patients with high-grade malignant brain tumors, including glioblastoma. This Phase 1b and Phase 2 study is part of the 5G-PEARL trial, which uses biomarker-guided approaches to treat tumors with specific genetic changes such as PI3K mutations or PTEN loss. The study aims to test these treatments in molecularly defined patient groups to better understand their effects. The study includes two parts Phase 1b focuses on safety and early activity, while Phase 2 assesses effectiveness further. In Phase 1b, patients receive paxalisib starting at 45 mg once daily, with a possible increase to 60 mg per day in Cycle 2. Temozolomide is taken orally once daily on days 1 to 5 of each 28-day cycle, starting at 150 mgm2 with potential dose increase to 200 mgm2 from Cycle 3 if tolerated. The trial enrolls patients into two biomarker arms based on tumor genetics, with adaptive decision points to guide study progress. Participants will have assessments including safety monitoring and genetic biomarker analysis over up to two years, depending on the phase. Researchers measure treatment-emergent adverse events and antitumor activity as primary outcomes. Quality of life and additional biomarker responses are also evaluated. Patients will be monitored regularly through clinical visits and tests to track treatment effects and side effects throughout the study duration.

5G-PEARL: Paxalisib in Malignant Brain Tumours