24VA021; VATCH Trametinib for Ras/MAPK Pathway VAs

Study Summary

The purpose of this study is to assess the effectiveness and safety of Trametinib (the "Study Drug") in patients with Ras/MAPK pathway driven vascular anomalies (VA). Trametinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma. Its use in this study is considered experimental because the FDA has not approved the study drug for treating people with VAs. The study will enroll participants 2 months of age up to 30 years of age that have been diagnosed with Ras/MAPK pathway driven vascular anomalies. Study participation will last up to 3 years and will involve regular study visits to Children's Hospital of Philadelphia (CHOP) Philadelphia Campus. Participants will need to take the study drug Trametinib for at least 2 years, or up to 3 years in total, if there is a positive response. Participating in this research means you will attend up to 16 clinic visits. Most visits will take approximately 30 minutes, but some visits will take approximately 2 hours, because you will be asked to complete questionnaires about your experience. Participating in this research also means taking the study drug, having pictures taken, and completing study drug diaries. There is also an optional portion to this study that involves collecting blood for biomarker testing.

Primary Outcome

Individualized Response is a composite outcome determined by the combined results of the following 3 distinct study assessments after cycle 6: Radiologic evaluation, PROMIS Patient reported outcome (PRO) measurements, and Clinical Benefit Assessments (CBA). The results of these 3 distinct assessments will be evaluated using a set of specific criteria to determine the Individualized Response to treatment (i.e. "Substantial Response" = Improvement in Radiologic assessment by 20%, AND improvement i

Interventions

• DRUG Trametinib