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.
Who can participate
Inclusion Criteria:
1. Signed informed consent and assent (when applicable)
2. Males or females age \> 2 months to \< 30 years at the time of informed consent.
3. Have a documented Ras/MAPK-pathway variant.
4. Have a symptomatic vascular anomaly in need of medical therapy.
5. Have a disease-related lesion or lesions which can be measured
6. Have a Lansky or Karnofsky performance status score of ≥ 50.
7. Have acceptable organ function
8. (For persons who can get pregnant) Have a negative serum or urine pregnancy test within 7 days prior to starting study medication.
9. Must agree to the use an acceptable method of contraception
10. Subjects must be able to swallow tablets or liquid or use a nasogastric or gastric tube
Exclusion Criteria:
1. Subjects seeking treatment for hypertrophic cardiomyopathy without a vascular anomaly
2. Prior medications that are not allowable per the study protocol
3. Confirmed or possible infections
4. History of hepatic sinusoidal obstructive syndrome (veno-occlusive disease of the liver) in the last 3 months.
5. Active gastrointestinal (GI) disease
6. Subjects with history of or current risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) or uncontrolled glaucoma or ocular hypertension.
7. Allergic reactions: Subjects with a history of allergic reaction attributed to compounds of similar chemical or biological composition to trametinib are not eligible.
8. History of prior and or ongoing cancer or ongoing investigations or treatment for cancer at time of informed consent.
9. Subjects unable to comply with safety monitoring requirements.
10. Subject may not be pregnant or breast feeding.
11. Parents/guardian/LAR or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
12. Debulking or other major surgery performed within 30 days, at time of informed consent;
13. Clinically meaningful bleeding related to VA: Grade 2 within 14 days or Grade 3 and more within 28 days before study treatment start as per CTCAE v. 5.0.
Sclerotherapy/embolization for vascular complications performed within 14 days before informed consent.
14. Subjects not able to understand and to comply with study instructions and requirements (in patients, legally authorized representatives, or guardians as applicable) at time of informed consent.
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