5G-PEARL: Paxalisib in Malignant Brain Tumours

NCT07391215 | Recruiting Phase 1

• 1 other identifier: CCR5814
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Primary Gliomas; Glioblastoma Multiforme (GBM)

Outcome Measures

Primary Outcomes (4)

• Phase 1b - Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) in patients with malignant brain tumours

  To identify the incidence, nature and severity of adverse events and laboratory abnormalities, with severity determined according to NCI CTCAE v5.0

  12 months

• Phase 1b - To determine the preliminary antitumour activity of the investigational agent administered at the RP2D in patients with molecularly defined malignant brain tumours

  Antitumour activity will be defined on the basis of the following outcomes. If any of the following occur, patients will be considered to have clinically benefitted: For front line unmethylated GBM (MRD): • Progression-free survival (PFS)

  12 months

• Phase 2 - To determine the antitumour activity of investigational agent administered at the RP2D in patients with molecularly defined malignant brain tumours

  Antitumour activity will be defined on the basis of the following outcome: • Progression-free survival (PFS), defined as the time from enrolment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RANO

  24 months

• Phase 2 - To determine the antitumour activity of investigational agent administered at the RP2D in patients with molecularly defined malignant brain tumours

  Antitumour activity will be defined on the basis of the following outcome: Overall survival (OS), defined as the time from enrolment to death from any cause

  24 months

Secondary Outcomes (7)

• Phase 1b - To identify genetic biomarkers of response in patients with molecularly selected brain tumours

  12 months

• Phase 2 - To identify genetic biomarkers of response in patients with molecularly selected brain tumours.

  24 months

• Phase 2 - To assess changes in Quality of Life over time

  12 months

• Phase 2 - To assess changes in Quality of Life over time

  6 months

• Phase 2 - Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of combination with TMZ when given as standard of care maintenance therapy

  24 months

Study Arms (2)

Phase 1b

EXPERIMENTAL

The Phase 1b will evaluate the safety and tolerability of paxalisib in combination with temozolomide and determine their preliminary antitumour activity in patients with molecularly defined malignant brain tumours.

Drug: Paxalisib; Drug: Temozolomide capsule

Phase 2

EXPERIMENTAL

The Phase 2 part of the study will determine the antitumour activity of investigational agents administered at the RP2D in patients with molecularly defined malignant brain tumours.

Drug: Paxalisib; Drug: Temozolomide capsule

Interventions

Paxalisib DRUG

Supplied as 15 mg capsules (35 capsules per bottle).

Also known as: GDC-0084

Phase 1b; Phase 2

Temozolomide capsule DRUG

Temozolomide will be supplied as 5, 20, 100, 140, 180 or 250 mg hard capsules.

Also known as: Temodal

Phase 1b; Phase 2

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1b front line mrd cohort:
• Patients with histologically confirmed advanced WHO Stage IV glioblastoma (per fourth edition 2016). Per the new 2021 fifth edition of WHO Classification of Tumours of the Central Nervous System, this will include:
• Glioblastoma, IDH-wildtype Grade 4
• Patients for Phase 1b will need to have consented to the Minderoo Precision Brain Tumour Programme and have whole genome, and transcriptome data available. Patients who have had NHS funded whole genome sequencing and have available frozen tissue stored can be recruited to the study in parallel to consenting to the Minderoo Precision Brain Tumour Programme to have transcriptome analysis done.

You may not qualify if:

• years or over.
• Life expectancy of at least 12 weeks.
• World Health Organisation (WHO) performance status of 0-1.
• Neurologically stable (eg without a progression of neurological symptoms or requiring escalating doses of systemic steroid therapy within one week prior to cycle 1, day 1.
• Written (signed or dated) informed consent and be capable of co-operating with treatment and follow up.
• Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week prior to the first dose of either IMP.
• Haemoglobin (Hb): ≥ 9.0 g/dL Absolute neutrophil count: ≥1.5 x 10\^9/L Platelet count: ≥100 x 10\^9/L Coagulation: INR \< 1.5 and APTT \<1.5x if not anticoagulated INR stable \> 7 days within intended therapeutic range if anticoagulated Bilirubin: ≤1.5 x ULN; participants with Gilbert's syndrome can enrol if conjugated bilirubin is within normal ranges.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST): \<3 x ULN Albumin: ≥ 28 g/L Creatinine: \<1.5 x ULN Sodium: ≥130 mmol/L Potassium, Calcium, Magnesium, phosphate: Within institution normal ranges (replacement is permitted) HbA1C (%): \<8.0 Urinary protein: \< 1+ on dipstick
• Female patients with reproductive potential must have a negative serum pregnancy test within 14 days prior to start of trial.
• Men and women of childbearing potential must agree to comply with the use of a highly effective method of contraception so as to avoid impregnating a partner or becoming pregnant, respectively, during the study, and for at least 180 days after the last dose of either investigational drug. Please, refer to section 4.1 of the Clinical Trials Facilitation and Coordination Group (CTCG) guidance for further details.
• Phase 1b frontline mrd cohort:
• Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:
• Bevacizumab during the prior 6 weeks
• Any investigational medicinal product since diagnosis.
• Tumour treating fields during the prior 6 weeks

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Minderoo Foundation: collaborator
• Kazia Therapeutics Limited: collaborator
• Royal Marsden NHS Foundation Trust: collaborator
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• Cancer Research UK: collaborator

Study Sites (1)

Royal Marden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

GDC-0084; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Juanita Lopez, MD, PhD

  National Health Service, United Kingdom

  STUDY DIRECTOR

Central Study Contacts

5G Team

CONTACT

0203 437 6003; 5G-enquiries@icr.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: February 5, 2026
• Study Start: January 19, 2026
• Primary Completion (Estimated): January 19, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: February 5, 2026

Record last verified: 2026-01

Locations

GB (1)