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

Sponsor
Murdoch Childrens Research Institute
Study ID
NCT05983159
Phase
PHASE2
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
2 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Alpelisib — DRUG
    Oral alpha-specific PI3-kinase inhibitor
  • Mirdametinib — DRUG
    An investigational oral MEK inhibitor

Study Details

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).

Key Dates

First listed
Aug 9, 2023
Start date
Sep 13, 2024
Status verified
Apr 2026
Primary completion
Jan 31, 2027
Completion
May 31, 2027

Study Design

Enrollment
50 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Module 1: Slow-flow vascular malformations
    Slow-flow vascular malformations with identified causative variants in the phosphoinositide 3-kinase (PI3K) signalling pathway will receive alpelisib (provided by Novartis Pharmaceuticals), an oral alpha-specific PI3-kinase inhibitor for a total duration of 48 weeks as monotherapy, followed by 24 weeks of follow-up.
  • Experimental: Module 2: Fast-flow vascular malformations
    Fast-flow vascular malformations with identified causative variants in the RAS-MEK-ERK signalling pathway will receive mirdametinib (provided by SpringWorks Therapeutics, Inc.), an investigational oral MEK inhibitor for a total duration of 48 weeks as monotherapy, followed by 24 weeks of follow-up.

Primary Outcome Measure

The number of participants who achieve or exceed a predetermined threshold of improvement in their most significant symptom at 48 weeks based on the Vascular Malformation Patient Specific Outcome Measure (VM-PSOM). [ Time Frame: At 48 weeks ]

Central Contacts

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