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New treatment option for Glioblastoma Multiforme (GBM)
Official title 5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours
ClinicalTrials.gov ID: NCT06630260
What this study is testing
What is Avutometinib?
Avutometinib is an investigational medicine, given as an once-weekly pill taken by mouth, being studied as a potential treatment for glioblastoma multiforme (gbm).
Also referred to as VS-6766.
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 avutometinib and defactinib and to determine the preliminary antitumour activity of avutometinib and defactinib administered at the recommended Phase 2 dose (RP2D). In the Phase 1b of this study parallel biomarker defined arms will be opened, initially in the relapsed GMB setting, enrolling 12 patients onto each arm.
- Phase 2: a mid-size study of how well it works
- Which group you join is decided by chance.
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
- for Phase 1b:
- 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
- Astrocytoma, IDH-mutant, Grade 4 (lower Grade 2/3 are not included)
- Diffuse hemispheric glioma, H3 G34 mutant Grade 4 Patients with any other CNS tumours will only be eligible for defined Phase 2 biomarker arms once a...
You likely can't join if
- 16 years or over
- Life expectancy of at least 12 weeks.
- World Health Organisation (WHO) performance status of 0-1
- Neurologically stable (e.g., without a progression of neurological symptoms or requiring escalating doses of systemic steroid therapy within the last...
- 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...
See the full eligibility criteria
Who can join
- for Phase 1b:
- 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
- Astrocytoma, IDH-mutant, Grade 4 (lower Grade 2/3 are not included)
- Diffuse hemispheric glioma, H3 G34 mutant Grade 4 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...
- Patients for Phase 1 will need to have consented to the Minderoo Precision Brain Tumour Programme and have available whole genome, and transcriptome data available.
- Patients for the relapsed cohorts will be eligible at first relapse following completion of optimal surgery, and Stupp based adjuvant chemo-radiotherapy (or equivalent). They will need to have measurable disease per...
- Patients for the front line 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
- 16 years or over
- Life expectancy of at least 12 weeks.
- World Health Organisation (WHO) performance status of 0-1
- Neurologically stable (e.g., without a progression of neurological symptoms or requiring escalating doses of systemic steroid therapy within the last week)
- 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 to avoid impregnating a partner or becoming pregnant, respectively, during the study, and for at...
- Receipt of treatment before the first dose of study drug (Cycle 1 Day 1) within an interval shorter than the following, as applicable:
- Cytotoxic chemotherapy during the prior 2 weeks or 6 weeks for nitrosoureas
- Bevacizumab during the prior 6 weeks
- Five half-lives of any small molecule investigational or licensed medicinal product.
- 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. Prior use of BRAF or MEK...
- 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 clinically 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 another significant thromboembolism. Venous port of catheter thrombosis or superficial thrombosis are not considered significant. Patients with...
- 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 ECG at Screening, including a corrected QT interval (QTcF \>460ms).
- History of malabsorption syndrome or other conditions that may interfere with enteral absorption. Patients with a history of or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis). Patients...
- Concurrent ocular disorders:
- Patients with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes
- Patient with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure \> 21 mm Hg as measured by tonometry, or other significant ocular...
- Patients with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions.
- 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.
- 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...
- Strong CYP3A4 inhibitors or inducers, due to potential drug-drug interactions with both avutometinib and defactinib.
- Strong CYP2C9 inhibitors or inducers, due to potential drug-drug interactions with defactinib. Not applicable if and when patients assigned by chance to avutometinib monotherapy.
- Strong P-glycoprotein (P-gp) inhibitors or inducers, due to potential drug-drug interactions with both avutometinib and defactinib.
- Strong breast cancer resistance protein (BCRP) inhibitors or inducers, due to potential drug-drug interactions with avutometinib.
- Major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 1 week of the first dose of defactinib.
- Any other condition which in the investigator's opinion would not make the patient a good candidate for the clinical trial.
The study team makes the final eligibility decision.
Where it's taking place
- Cambridge, United Kingdom
- 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 Cambridge, United Kingdom; 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.