Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06630260
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-10-03
Brief Title:
5G-RUBY Avutometinib and Defactinib in Malignant Brain Tumours
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Phase 12 Trial of the Doublet Combination of Avutometinib and Defactinib and As a Triplet in Combination with Temozolomide in Patients with High Grade Malignant Brain Tumours Within the 5G Platform
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
5G-RUBY
Brief 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 32mg twice a week eg on Monday Thursday or Tuesday Friday with or without a meal The total weekly dose of avutometinib is 64mg 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 successes12 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
Once a treatment in any biomarker arm has met the GO decision 3 successes12 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
Detailed Description:
The clinical trial will be divided into two parts Phase 1b proof of concept of hypothesis-driven biomarker-guided therapies and Phase 2 preliminary efficacy testing
This is a study within Minderoo 5G A Next Generation AGile Genomically Guided Glioma Modular Platform for proof-of-concept molecular hypothesis testing in patients with high grade malignant brain tumours
5G-RUBY is a Bayesian multi-centre multi-arm open-label adaptive seamless Phase 12 trial of doublet combination of avutometinib and defactinib and triplet combination with temozolomide for patients with malignant brain tumours
5G-RUBY will recruit patients with glioblastoma GBM into two molecularly-defined biomarker arms of patients who have tumours that harbour
Hyperactivating BRAF mutations or fusions predicted to be pathogenic by COSMIC
NF1 loss
Each biomarker arm within Phase 1 will have robust GOADAPT decision points reviewed by the Safety Review Committee SRC to allow for both agility and clear direction for next steps A 2-stage Bayesian adaptive design will be performed to assess preliminary efficacy
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 with a total weekly dose of 64mg and defactinib with a total daily dose of 400mg
Phase 2 efficacy testing will be undertaken in the front line adjuvant MRD setting This can be either as double combination or in triple combination with temozolomide concomitantly or sequentially depending on emerging data Further details will be provided at once the SRC has assessed data from Phase 1 and formally opened Phase 2
This is a study within Minderoo 5G A Next Generation AGile Genomically Guided Glioma Modular Platform for proof-of-concept molecular hypothesis testing in patients with high grade malignant brain tumours
5G-RUBY is a Bayesian multi-centre multi-arm open-label adaptive seamless Phase 12 trial of doublet combination of avutometinib and defactinib and triplet combination with temozolomide for patients with malignant brain tumours
5G-RUBY will recruit patients with glioblastoma GBM into two molecularly-defined biomarker arms of patients who have tumours that harbour
Hyperactivating BRAF mutations or fusions predicted to be pathogenic by COSMIC
NF1 loss
Each biomarker arm within Phase 1 will have robust GOADAPT decision points reviewed by the Safety Review Committee SRC to allow for both agility and clear direction for next steps A 2-stage Bayesian adaptive design will be performed to assess preliminary efficacy
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 with a total weekly dose of 64mg and defactinib with a total daily dose of 400mg
Phase 2 efficacy testing will be undertaken in the front line adjuvant MRD setting This can be either as double combination or in triple combination with temozolomide concomitantly or sequentially depending on emerging data Further details will be provided at once the SRC has assessed data from Phase 1 and formally opened Phase 2
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None