Actively Recruiting
A Phase 1/2 Trial of Avutometinib and Defactinib with or without Temozolomide in Patients with High Grade Malignant Brain Tumours Within the 5G Platform
Led by Institute of Cancer Research, United Kingdom · Updated on 2026-01-21
182
Participants Needed
3
Research Sites
52 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
Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of two investigational drugs, avutometinib and defactinib, in patients with high grade malignant brain tumours, including glioblastoma (GBM). This Phase 1/2 clinical trial uses biomarker-guided approaches to target specific molecular subtypes of brain tumours. The study is part of the Minderoo 5G platform and includes patients with relapsed or frontline minimal residual disease (MRD) settings. In Phase 1b, patients with relapsed GBM will receive oral avutometinib at a dose of 3.2 mg twice weekly and defactinib at 200 mg twice daily after meals, aiming for a total weekly dose of 6.4 mg and daily dose of 400 mg respectively. Phase 2 will test the antitumour activity of these drugs given at the recommended dose, either as a doublet or combined with temozolomide, depending on earlier results. Treatment will be given in molecularly defined biomarker arms, with decisions guided by safety and efficacy data. Participants will undergo assessments for safety, tolerability, and tumour response over 9 to 12 months. Molecular profiling will help identify response markers, and quality of life will be monitored during Phase 2. Patients must consent to genomic testing and will be followed regularly with clinical evaluations. The study includes rigorous monitoring for side effects and disease progression, with a total participation duration aligned with treatment phases and follow-up.
CONDITIONS
Brief Title
5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients aged 16 years or older
- Histologically confirmed advanced WHO Stage IV glioblastoma or related high grade brain tumours
- Consent to genomic testing with available whole genome and transcriptome data
- Patients at first relapse after surgery and chemo-radiotherapy or in front line minimal residual disease setting
- Life expectancy of at least 12 weeks
- WHO performance status of 0-1
- Neurologically stable without recent worsening symptoms or increased steroid use
- Hematological and biochemical blood tests within specified ranges prior to treatment
- Negative pregnancy test for women with reproductive potential
- Agreement to use effective contraception during and after the study
You will not qualify if you...
- Recent cancer treatments: chemotherapy within 2 weeks or 6 weeks for nitrosoureas, bevacizumab within 6 weeks
- Prior immune checkpoint inhibitors, vaccines, BRAF or MEK inhibitors
- Ongoing Grade 2 or higher toxicities from prior treatments or conditions
- Presence of carcinomatous meningitis, tumour spread to brain stem or spinal cord
- Recent or ongoing tumour hemorrhage on MRI
- History of significant bleeding disorders or arterial thromboembolism
- Recent deep vein thrombosis or pulmonary embolism within 3 months
- Significant cardiac disorders or abnormal ECG findings
- Gastrointestinal conditions affecting drug absorption or inflammatory bowel disease
- Concurrent ocular disorders including glaucoma or retinal problems
- Proteinuria exceeding specified limits
- Significant lung diseases or history of certain infections
- Positive for hepatitis B, C, or HIV
- Steroid use exceeding 3mg dexamethasone daily unless stable dose
- Recent live vaccines within 30 days
- Active concurrent malignancy except certain cancer survivors
- Participation in other interventional trials
- Use of medications that interact with study drugs within 14 days
- Major surgery within 4 weeks, minor surgery within 2 weeks, or recent radiotherapy
- Any other condition judged unsuitable by the investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 12 months in Phase 1b or up to 9 months in Phase 2
Participants receive treatment with a combination of avutometinib and defactinib, with or without temozolomide, according to their assigned study phase and molecular biomarker arm.
Regular visits for treatment and monitoring as per protocol
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
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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