5G-PEARL: Paxalisib in Malignant Brain Tumours
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age16+
SponsorInstitute of Cancer Research, United Kingdom
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Patients for the minimal residual disease (mrd) cohort will be eligible following completion of optimal surgery and Stupp based adjuvant chemoradiotherapy as long as they meet all other inclusion/
Disqualifiers
16 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.
Trial design
Design model
Parallel
Treatments tested in this trial
Paxalisib
DrugSupplied as 15 mg capsules (35 capsules per bottle).
Temozolomide capsule
DrugTemozolomide will be supplied as 5, 20, 100, 140, 180 or 250 mg hard capsules.
Treatment groups
64 Participants
are divided into 2 treatment groupsGroup A: Phase 1bExperimental treatment 2 interventions
Group B: Phase 2Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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
Time frame
12 months2
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)
Time frame
12 months3
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
Time frame
24 months4
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
Time frame
24 monthsSecondary outcomes
1
Phase 1b - To identify genetic biomarkers of response in patients with molecularly selected brain tumours
Determine co-occurring genetic biomarkers predicting response.
Time frame
12 months2
Phase 2 - To identify genetic biomarkers of response in patients with molecularly selected brain tumours.
Determine co-occurring genetic biomarkers predicting response.
Time frame
24 months3
Phase 2 - To assess changes in Quality of Life over time
OS12, defined as the percentage of patients who remained free of death at 12 months from study enrolment
Time frame
12 months4
Phase 2 - To assess changes in Quality of Life over time
PFS6, defined as the percentage of patients who remained free of disease progression 6 months from study enrolment
Time frame
6 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Institute of Cancer Research, United Kingdom
Lead sponsor
Minderoo Foundation
Collaborator
Kazia Therapeutics Limited
Collaborator
Royal Marsden NHS Foundation Trust
Collaborator
Cambridge University Hospitals NHS Foundation Trust
Collaborator
Cancer Research UK
Collaborator
Source ClinicalTrials.gov