NCT05983159

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

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: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Murdoch Childrens Research Institute · Academic / Other
• Sex: All
• Age: 2 Years
• Healthy volunteers: Not accepted

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).

Detailed 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.

Conditions

• Slow-Flow Vascular Malformation
• Fast-Flow Vascular Malformation
• Vascular Malformations
• Venous Malformation
• Lymphatic Malformation, Low Flow
• Lymphatic Malformation
• Lymphangioma
• Arteriovenous Malformations
• Venous Malformation, Low Flow
• Cystic Hygroma
• Vascular Anomaly
• Vascular Anomalies
• PI3K Gene Mutation
• MAP2K1 Gene Mutation
• PIK3CA-related Overgrowth Spectrum
• Arteriovenous Malformation (AVM)
• KRAS G12C
• KRAS G12D

Interventions

Type	Name	Description
DRUG	Alpelisib	Oral alpha-specific PI3-kinase inhibitor
DRUG	Mirdametinib	An investigational oral MEK inhibitor

Timeline

• Start date: 2024-09-13
• Primary completion: 2026-08-01
• Completion: 2026-12-01
• First posted: 2023-08-09
• Last updated: 2026-02-19

Locations

2 sites across 1 country: Australia

Regulatory

• FDA-regulated drug study