5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours (NCT06630260) | Clinical Trial Compass
RecruitingPhase 1/2
5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours
United Kingdom182 participantsStarted 2024-11-15
Plain-language summary
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.
Who can participate
Age range16 Years
SexALL
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Inclusion criteria
✓. 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:
✓. 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 RANO or evaluable disease.
Exclusion criteria
✕. 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
What they're measuring
1
Phase 1b - To evaluate the safety and tolerability of investigational agent in patients with malignant brain tumours
Timeframe: 12 months
2
Phase 1b - To determine the preliminary antitumour activity of the investigational agent administered at the RP2D in patients with molecularly defined malignant brain tumours
Timeframe: 12 months
3
Phase 2 - To determine the antitumour activity of investigational agent administered at the RP2D in patients with molecularly defined malignant brain tumours
Timeframe: 9 months
Trial details
NCT IDNCT06630260
SponsorInstitute of Cancer Research, United Kingdom
✕0. 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
✕1. Female patients with reproductive potential must have a negative serum pregnancy test within 14 days prior to start of trial.
✕2. 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 least 150 days after the last dose of either investigational drug.