A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations — TARGET-VM  

Arteriovenous Malformations Clinical Trial

Official title: A Modular Open Label, Signal Seeking, Phase II Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations (TARGET-VM)

Status Not yet recruiting

Clinical Trial Summary

Recent studies have demonstrated that growth of vascular malformations can be driven by genetic variants in one of 2 signalling pathways. Targeted drugs specific to these pathways have been developed and shown to be effective in treating cancer. This study will describe the effectiveness of (i) 48 weeks of alpelisib therapy for participants with slow-flow vascular malformations and a gene mutation in one of these signalling pathways (module 1) and (ii) 48 weeks of mirdametinib therapy for participants with fast-flow vascular malformations and a gene mutations in the other signalling pathway (module 2).

Clinical Trial Description

TARGET-VM is a modular open-label, signal seeking, phase II trial of targeted therapies for patients with vascular malformations. Patients with vascular malformations which are refractory to standard therapies, or in whom standard therapy is not appropriate, are potentially eligible for the clinical trial. Vascular malformations will be classified as slow-flow or fast-flow lesions using established clinical criteria. Genetic testing to identify causative variants in genes affecting the phosphoinositide 3-kinase (PI3K) signalling pathway for slow-flow vascular malformations or the Mitogen-Activated Protein Kinase (MAPK) signalling pathway for fast-flow vascular malformations must be performed using research protocols or commercial testing assays that are external to this clinical trial.

The study consists of individual modules, each evaluating the clinical efficacy of 48 weeks of targeted therapy. The treatment modules are:

1. Module 1 - Treatment for slow-flow vascular malformations Eligible patients with slow-flow vascular malformations with an identified causative variant in the PI3K signalling pathway will receive alpelisib, an oral alpha-specific PI3-kinase inhibitor for a total duration of 48 weeks as monotherapy (treatment period), followed by 24 weeks of follow-up (follow-up period).

2. Module 2 - Treatment for fast-flow vascular malformations Eligible patients with fast-flow vascular malformations with an identified causative variant in the MAPK signalling pathway will receive mirdametinib, an investigational oral MEK inhibitor for a total duration of 48 weeks as monotherapy (treatment period), followed by 24 weeks of follow-up (follow-up period).

TARGET-VM will be conducted only in Victoria, Australia. ;

Related Conditions & MeSH terms

• Arteriovenous Malformations
• Congenital Abnormalities
• Hemangioma
• KRAS G12D
• Lymphangioma
• Lymphatic Abnormalities
• Lymphatic Malformation
• MAP2K1 Gene Mutation
• PI3K Gene Mutation
• Vascular Anomalies
• Vascular Anomaly
• Vascular Malformations
• Venous Malformation

• NCT number: NCT05983159
• Study type: Interventional
• Source: Murdoch Childrens Research Institute
• Contact: Michelle de Silva, PhD
• Phone: +61399366109
• Email: michelle.desilva@vcgs.org.au
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 2024
• Completion date: December 2026