Trametinib in Treating Patients With Epithelioid Hemangioendothelioma That is Metastatic, Locally Advanced, or Cannot Be Removed by Surgery

Inclusion Criteria

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; baseline imaging must be obtained within 30 days of day 1 of study
• Patients must have histologically confirmed epithelioid hemangioendothelioma which is metastatic or locally advanced (unresectable), and tumor tissue (paraffin-embedded tissue block or tumor tissue on unstained glass slides) available for fusion fluorescence in situ hybridization (FISH) analysis at Cleveland Clinic; patient tumor tissue stored in pathology archives may be used for fusion FISH; a new biopsy is not mandatory
• Patients must have evidence of disease progression per RECIST 1.1 prior to enrollment or have evidence of cancer-related pain requiring symptom management with narcotic analgesics
• Because there is no established standard or approved drug therapy for treatment of epithelioid hemangioendothelioma (EHE), patients previously untreated or treated with drug therapy for EHE are eligible; there is no limit on the number of prior regimens used to be eligible
• Eastern Cooperative Oncology Group (ECOG) performance status = = 60%)
• Life expectancy of greater than 6 months
• Able to swallow orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or small bowel
• All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5) grade = = 1 x 10^9/L (within 2 weeks of patient registration)
• Hemoglobin >= 9 g/dL, patients may receive transfusion to meet criterion (within 2 weeks of patient registration)
• Platelets >= 75 x 10^9/L (within 2 weeks of patient registration)
• Albumin >= 2.5 g/dL (within 2 weeks of patient registration)
• Total bilirubin = = 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min (within 2 weeks of patient registration)
• Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA) (within 30 days of registration)
• Trametinib can cause fetal harm when administered to a pregnant woman; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the study participation, and for four months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to enrollment and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Human immunodeficiency virus (HIV)-patients positive for human immunodeficiency virus (HIV) are NOT excluded from this study, however HIV-positive patients must meet the following criteria:
• A stable regimen of highly active anti-retroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
• A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based test

Exclusion Criteria

• Prior systemic therapy with a MEK inhibitor
• History of another malignancy
• Exception: patients who have been disease-free for 3 years or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult th