A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
Trial Parameters
Brief 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).
Eligibility Criteria
MODULE 1 Inclusion Criteria: 1. Adult or paediatric patient, 2 years of age or over 2. Patient has a clinical diagnosis of a slow-flow vascular malformation 3. Patient has received standard therapy for the vascular malformation or in which, in the opinion of the investigator, standard therapy is not appropriate \- Note: standard therapy may include treatment with sirolimus. A minimum of 14 days since the last dose of sirolimus is required prior to starting treatment with alpelisib 4. A documented genetic alteration in the PI3K signalling pathway identified by genetic sequencing prior to enrolment in this study 5. Adequate performance status (Eastern Cooperative Oncology Group Performance Status Scale (ECOG) 0-2 in patients ≥ 16 years of age; Lansky \> 50 in patients \< 16 years of age) 6. Patient has a life expectancy ≥ 12 weeks 7. Patient is able to swallow and retain oral medication 8. Adequate haematologic and end-organ function: * Haematology: Haemoglobin ≥ 9.0 g/dL; Absolute neutr