Actively Recruiting
5G-PEARL: Paxalisib in Combination With Temozolomide in Patients With High Grade Malignant Brain Tumours Within the 5G Platform
Led by Institute of Cancer Research, United Kingdom · Updated on 2026-02-05
64
Participants Needed
1
Research Sites
23 weeks
Total Duration
On this page
Sponsors
I
Institute of Cancer Research, United Kingdom
Lead Sponsor
M
Minderoo Foundation
Collaborating Sponsor
AI-Summary
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 mg/m2 with potential dose increase to 200 mg/m2 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.
CONDITIONS
Brief Title
5G-PEARL: Paxalisib in Malignant Brain Tumours
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients aged 16 years or older
- Histologically confirmed advanced WHO Stage IV glioblastoma, including glioblastoma, IDH-wildtype Grade 4
- Consent to the Minderoo Precision Brain Tumour Programme with available whole genome and transcriptome data
- Completion of optimal surgery and Stupp-based adjuvant chemoradiotherapy with no radiological progression
- Ability to start Cycle 1 Day 1 within 6 weeks of completing chemoradiotherapy
- Life expectancy of at least 12 weeks
- WHO performance status of 0-1
- Neurologically stable without recent worsening symptoms or increasing steroid dose
- Adequate blood counts and organ function within specified ranges
- Negative pregnancy test for females with reproductive potential
- Agreement to use effective contraception during the study and for 180 days after last dose
- Signed informed consent and ability to cooperate with treatment and follow-up
You will not qualify if you...
- Receipt of bevacizumab, investigational medicinal products, or tumor treating fields within specified prior intervals before study drug
- Prior immune checkpoint inhibitor or vaccine therapy; other immune-modulatory agents require discussion
- Ongoing Grade 2 or higher toxicities from previous conditions or treatments
- Presence of carcinomatous meningitis, leptomeningeal tumor spread, or spread to brain stem or spinal cord
- Recent intratumoural or peritumoural hemorrhage on baseline MRI without stable consecutive scans
- History of significant bleeding disorders or arterial thromboembolism
- Recent deep vein thrombosis, pulmonary embolism, or significant thromboembolism within 3 months
- Significant cardiac disorders or abnormal ECG including prolonged QTcF
- Malabsorption syndrome or inflammatory bowel disease
- Uncontrolled diabetes or urine protein over 1g/24 hours
- Significant lung diseases or history of opportunistic infections
- Positive for hepatitis B, C, or HIV
- Steroid use above 3mg dexamethasone daily unless stable for 5 days
- Live vaccine within 30 days before study; inactive vaccines allowed
- Active concurrent malignancy unless cured and no recurrence for 3 years
- Participation in other interventional clinical trials during this study
- Use of medications or supplements with potential interactions within 14 days before first dose
- Recent major or minor surgery within 4 or 2 weeks respectively
- Live and attenuated vaccines not permitted during or within 4 weeks before treatment start
- Any other condition deemed unsuitable by investigator for study participation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 12 months
Participants receive paxalisib in combination with temozolomide in 28-day cycles to evaluate safety, tolerability, and preliminary antitumour activity.
Multiple visits during treatment cycles
Duration - Up to 24 months
Participants are monitored for long-term antitumour activity, safety, and quality of life after treatment completion.
Periodic follow-up visits
Trial Site Locations
Total: 1 location
1
Royal Marden NHS Foundation Trust
Sutton, United Kingdom, SM2 5PT
Actively Recruiting
Research Team
5
5G Team
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
HEALTH_SERVICES_RESEARCH
Number of Arms
2
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