Dr. Eric Sandler, M.D.

Topical Rapamycin/Sirolimus

for Vascular Anomalies

Proposed Study: Treatment protocol for the use of the topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and other susceptible lesions 1. Aim The aim of this treatment study is to evaluate the benefit and tolerability of topical sirolimus applied to cutaneous vascular anomalies in pediatric patients. The primary end point will be individually determined based on improvement in lesional clinical characteristics over baseline 2. Rationale for topical sirolimus use in VA The rationale for the use of topical sirolimus is to minimize these potential side effects and risks. Data for the use of topical sirolimus for vascular anomalies at this time are anecdotal and case reports only. As such, this prospective protocol seeks to determine the effectiveness and tolerability of topical sirolimus on patients with vascular anomalies that have a cutaneous component. 3. Experimental design This is an open-labeled efficacy trial with the aim to determine if topical sirolimus can be safe and efficacious in treating the cutaneous component of complicated vascular anomalies. Patients who meet eligibility criteria with a diagnosis of vascular anomaly (VA) with cutaneous component will be offered treatment with the investigational topical sirolimus. Patients will receive topical sirolimus therapy for a total of six months and will be monitored regularly at the research site for clinical response. Response will be based on pre-determined clinical criteria. Patients will be removed from study if there is no response at three months after initiation of therapy. Clinical response will be defined as improvement in measurable parameters defined at the time of initiation of therapy. These include 1. Size of lesions, measured in two parallel longest diameters 2. Flattening of lesion 3. Number of vesicles 4. Episodes of superinfection or bleeding 5. Improvement in pain 4. Drug Information The topical sirolimus formulation will be made at a concentration of 1% sirolimus ointment. Bulk sirolimus powder will be compounded in a liposomal base in a GMP level pharmaceutical company. This base will enhance drug penetration into the skin. It ensures adequate adhesion to the application area and a low degree of systemic absorption. Due to limited absorption only mild side effects are expected.