5G-PEARL: Paxalisib in Malignant Brain Tumours

The purpose of this clinical trial is to evaluate the safety and tolerability of paxalisib in combination with temozolomide and to determine the preliminary antitumour activity of the combination therapy. In the Phase 1b of this study parallel biomarker defined arms will be opened in the front-line unmethylated MGMT setting, enrolling 10 patients onto each arm. These patients will be treated with paxalisib in combination with temozolomide (TMZ). The starting dose of paxalisib will be 45mg once a day (OD) with the option of increasing to 60 mg (30 mg BD) in Cycle 2. TMZ will be administered once daily by mouth on days 1 to 5 in a 28-day cycle, with a starting dose of 150mg/m2 during cycles 1 and 2, and subsequent dose escalation to 200mg/m2 at the start of cycle 3 if cycles 1 and 2 have been well tolerated with no significant toxicity.

NCT Number	NCT07391215
Lead Sponsor	Institute of Cancer Research, United Kingdom Collaborators: Minderoo Foundation, Kazia Therapeutics Limited, Royal Marsden NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Cancer Research UK
Conditions	Malignant Primary Gliomas, Glioblastoma Multiforme (GBM)
Enrollment	64 participants
Start Date	2026-01-19
Primary Completion	2029-01-19 (estimated)
Study Completion	2029-06-30 (estimated)
Updated on ClinicalTrials.gov	2026-02-05