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New treatment option for Malignant Primary Gliomas
Official title 5G-PEARL: Paxalisib in Malignant Brain Tumours
ClinicalTrials.gov ID: NCT07391215
What this study is testing
What is Paxalisib?
Paxalisib is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for malignant primary gliomas.
Also referred to as GDC-0084.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 16 and older
You may be able to join 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...
- 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...
- Patients for the minimal residual disease (mrd) cohort will be eligible following completion of optimal surgery and Stupp based adjuvant...
You likely can't join if
- . Patients will need to commence Cycle 1 Day 1 of the study no later than 6 weeks from the completion of chemoradiotherapy. Patients who are...
- 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...
- Written (signed or dated) informed consent and be capable of co-operating with treatment and follow up.
See the full eligibility criteria
Who can join
- 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...
- 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/
What rules you out
- . Patients will need to commence Cycle 1 Day 1 of the study no later than 6 weeks from the completion of chemoradiotherapy. Patients who are radiologically progressing following chemo-radiotherapy will not be eligible.
- 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.
- 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...
- 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...
- 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
- Prior immune checkpoint inhibitor therapy or vaccine therapy is not permitted. Prior use of any other immune-modulatory investigational agent must be discussed with sponsor team and CI.
- Ongoing Grade 2 or greater toxicities from pre-existing conditions or from previous treatments.
- Patients with carcinomatous meningitis, leptomeningeal spread of tumour, spread of tumour to the brain stem or spinal cord.
- Has evidence of recent intratumoural or peritumoural haemorrhage on baseline MRI. Patients with radiological findings that are stable on at least 2 consecutive MRI scans at least 3 weeks apart will be eligible.
- History of clinical relevant bleeding disorders, including significant GI bleeding within last 6 months.
- History of arterial thromboembolism.
- Recent (within 3 months) deep vein thrombosis or pulmonary embolism or other significant thromboembolism. Venous port of catheter thrombosis or superficial thrombosis are not considered significant. Patients with prior...
- History of clinically significant cardiac disorders:
- Myocardial infarction, or New York Heart Association Class II to IV congestive heart failure, within 6 months of the first dose of study drug.
- Concurrent and clinically significant abnormalities on electrocardiogram (ECG) at Screening, including a corrected QT interval (QTcF \>480ms).
- History of malabsorption syndrome or other conditions that may interfere with enteral absorption. Patients with a history of or active inflammatory bowel disease (eg Crohn's disease or ulcerative colitis). History of...
- History of uncontrolled diabetes. Patients with controlled diabetes on therapy with HbA1C \<8% will be eligible.
- Has urine protein \> 1g/24 hours. Participants with \>1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria.
- Has significant lung disease including pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, active tuberculosis, or history of opportunistic infections (including PCP or CMV pneumonia).
- Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
- Steroid requirement for neurological symptom control of \>3mg Dexamethasone per day (patients will allowed to enrol if they have been on a stable dose of steroids of equivalent or less than 3mg Dexamethasone for at...
- Has received a live vaccine within 30 days of planned start of study therapy. Note: inactive vaccines including COVID vaccines are allowed prior to 1 week of Day 1 of Cycle 1).
- Current active concurrent malignancy. Cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease recurrence for three years or more and are deemed at...
- Is a participant or plans to participate on another treatment clinical trial while taking part in this Phase 1 study. Participation in an observational trial would be acceptable.
- Any other condition which in the investigator's opinion would not make the patient a good candidate for the clinical trial.
- Exposure to medications (with or without prescriptions), supplements, herbal remedies, or foods with potential for drug-drug interactions with study interventions within 14 days prior to the first dose of study...
- Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks.
- Live and attenuated vaccines are not permitted during or within 4 weeks prior to initiation of study treatment. Inclusion and Exclusion criteria for Phase 2:
- This will be broadened following an assessment of the safety and side effects seen in the Phase 1 to be more inclusive and reflective of the real-world population.
- Patients with any other CNS tumours will only be eligible for defined Phase 2 biomarker arms once a Phase 1b GO decision has been met. Specific eligibility criteria for these tumours will be defined following an...
The study team makes the final eligibility decision.
Where it's taking place
- Sutton, United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 16 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Sutton, United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.