Actively Recruiting
5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours
Led by Institute of Cancer Research, United Kingdom · Updated on 2026-01-21
182
Participants Needed
3
Research Sites
306 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
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. These patients will be treated with avutometinib and defactinib double therapy. Avutometinib will be administered orally at 3.2mg twice a week (e.g., on Monday / Thursday or Tuesday / Friday) with or without a meal. The total weekly dose of avutometinib is 6.4mg. Defactinib will be administered orally, at 200mg, twice a day within 30 min after a meal. The total daily dose of defactinib is 400mg. Once a treatment in any biomarker arm has met the "GO" decision (≥3 successes/12 patients) for relapsed GBM in Phase 1b, that arm can progress to Phase 2. The primary objective of Phase 2 is to determine the antitumour activity of investigational agents administered at the RP2D in patients with molecularly defined malignant brain tumours.
CONDITIONS
Official Title
5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients with histologically confirmed advanced WHO Stage IV glioblastoma, including glioblastoma IDH-wildtype Grade 4, astrocytoma IDH-mutant Grade 4, or diffuse hemispheric glioma H3 G34 mutant Grade 4
- Patients must have consented to the Minderoo Precision Brain Tumour Programme and have whole genome and transcriptome data available
- Patients with relapsed disease at first relapse after surgery and Stupp-based chemo-radiotherapy or equivalent, with measurable or evaluable disease
- Patients in front line minimal residual disease cohort after surgery and Stupp-based chemoradiotherapy
- Age 16 years or older
- Life expectancy of at least 12 weeks
- WHO performance status of 0 or 1
- Neurologically stable without progression of symptoms or increasing steroid dose in the past week
- Written informed consent and ability to cooperate with treatment and follow-up
- Adequate blood counts and liver/kidney function within specified ranges within one week before first study drug dose
- Negative serum pregnancy test within 14 days before trial start for females with reproductive potential
- Agreement to use highly effective contraception during the study and for 150 days after last dose for men and women of childbearing potential
You will not qualify if you...
- Recent cytotoxic chemotherapy within 2 weeks (6 weeks for nitrosoureas) before first study drug dose
- Bevacizumab within 6 weeks before first dose
- Prior immune checkpoint inhibitor or vaccine therapy; prior BRAF or MEK inhibitor use not permitted
- Ongoing Grade 2 or higher toxicities from previous conditions or treatments
- Presence of carcinomatous meningitis, leptomeningeal spread, or tumor spread to brain stem or spinal cord
- Recent intratumoural or peritumoural hemorrhage on baseline MRI unless stable on two MRIs 3 weeks apart
- History of significant bleeding disorders or arterial thromboembolism
- Recent deep vein thrombosis, pulmonary embolism, or significant thromboembolism within 3 months
- Significant cardiac disorders including recent myocardial infarction or congestive heart failure
- Malabsorption syndrome, inflammatory bowel disease, pancreatitis, gastrointestinal perforation or fistulae, or Gilbert's syndrome
- Certain ocular disorders including glaucoma, retinal vein occlusion risk factors, or serious ocular surface inflammatory conditions
- Urine protein over 1 g/24 hours
- Significant lung disease or history of opportunistic infections
- Seropositive for hepatitis B, hepatitis C, or HIV
- Steroid use over 3 mg dexamethasone per day for neurological symptom control unless stable dose for 5 days prior
- Live vaccine within 30 days before study therapy start
- Active concurrent malignancy except certain cancer survivors
- Participation in another interventional clinical trial during this study
- Use of medications or substances with potential drug interactions with study drugs within 14 days before first dose
- Major surgery within 4 weeks, minor surgery within 2 weeks, or palliative radiotherapy within 1 week before first dose
- Any other condition making the patient unsuitable for the trial in the investigator's opinion
AI-Screening
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Trial Site Locations
Total: 3 locations
1
Cambridge University Hospitals
Cambridge, United Kingdom, CB2 0QQ
Actively Recruiting
2
The Royal Marsden Hospital - Drug Development Unit
Sutton, United Kingdom, SM2 5PT
Actively Recruiting
3
The Royal Marsden Hospital - Neuro-Oncology Unit
Sutton, United Kingdom, SM2 5PT
Actively Recruiting
Research Team
5
5G Team
CONTACT
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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