Clinical Research Directory

A Study to Evaluate the Efficacy and Safety of Everolimus in Patients With Teratment-refractory Vascular Anomalies

Background and Objectives Vascular anomalies are a heterogeneous group of disorders classified into vascular tumors and vascular malformations according to the ISSVA classification. Although most follow a benign course, a subset causes serious complications including organ dysfunction, chronic pain, thrombocytopenia, and hemorrhage. Kaposiform hemangioendothelioma (KHE) complicated by Kasabach-Merritt Phenomenon (KMP) carries a mortality rate of 14-24%. Surgical resection is the primary treatment when organ damage is not anticipated; however, when surgery is not feasible, pharmacologic therapy is considered. Agents such as interferon, corticosteroids, vincristine, cyclophosphamide, and propranolol have been used with variable efficacy, and no established therapy exists for patients refractory to these treatments. The PI3K-Akt-mTOR and RAS-MEK-ERK pathways have been identified as key molecular mechanisms underlying vascular anomalies. Targeted therapies against these pathways are emerging, including anti-VEGF antibodies, PI3K/Akt inhibitors (e.g., alpelisib, miransertib), and mTOR inhibitors. Sirolimus has demonstrated clinical benefit in 50-80% of patients with vascular anomalies, with a 96% symptom response rate in KMP-associated vascular tumors. Everolimus, another mTOR inhibitor, is already approved and established for tuberous sclerosis-associated angiomyolipoma and SEGA in pediatric patients, with a well-characterized safety profile. Given its shared mechanism with sirolimus and emerging case reports supporting efficacy in KHE with KMP, this phase 2 study aims to evaluate the efficacy and safety of everolimus in patients with treatment-refractory vascular anomalies. Study Design This is a single-center, open-label, uncontrolled phase 2 clinical trial enrolling 67 patients over 60 months from IRB approval, stratified into two cohorts: Cohort 1 (sirolimus-naïve, n=39) and Cohort 2 (prior sirolimus failure, n=28). Everolimus is administered orally at age- and CYP3A4/P-gp inducer-adjusted doses, with maintenance dosing titrated to a target trough level of 5-15 ng/mL. The primary endpoint is overall response rate (ORR) at 6 months. Secondary endpoints include toxicity per NCI CTCAE v4.0, ORR at 12 months, platelet recovery rate at 4 weeks (KMP patients), 1-year overall survival, and 3-year progression-free survival.

Weekly Sirolimus Therapy

In current practice, options for venous and lymphatic malformations remain limited. Recently an oral medication, sirolimus, has been found to benefit patients when taken once or twice a day for several months. Unfortunately there are many side effects associated with this medication, some of which can be severe including, neutropenia, oral ulcerations, and lab abnormalities. The purpose of this study is to determine if once weekly dosed sirolimus will be effective for the treatment of venous and lymphatic malformations. Additionally, the study will evaluate patient satisfaction and identify adverse effects. Participants will be on the medication for 6 months with an option to continue after this time period.

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

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).

Efficacy and Safety Analysis of Polylauric Alcohol More Stable Foam Versus Ordinary Foam in the Treatment of Head and Neck Venous Malformations

The aim of this study is to explore the efficacy and safety of poly -LRB-cinnamyl alcohol) foam in the treatment of venous malformations of head and neck through a prospective randomized clinical trial, this trial may provide better treatment options and evidence for head and neck VMs.

A Study of Enalapril in Treatment of Venous Malformations

The goal of this clinical trial is to explore if enalapril can be used to treat painful venous malformations. The main question it aims to answer are: \- Can enalapril reduce pain and volume of the malformation and increase quality of life in patients with painful venous malformations? Participants will: Receive a dose of enalapril 5 mg once daily. If it doesn't have effect the dose of enalapril will be increased to 10 mg daily after 3 months. The treatment duration will be 12 months, with an additional follow-up of 12 months. The visit frequency will be after 1, 3, 6,9 and 12 months and then a follow up visit at 18 and 24 months. Approximately 15 participants will be screened to achieve minimum 10 enrolled participants.