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Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation
Trial ID: NCT04258046
Arteriovenous malformation (AVM) is a congenital vascular anomaly that progresses throughout life and causes complications including tissue destruction due to rapid overgrowth, bleeding, functional deficits, severe deformity and cardiac failure. Unfortunately, traditional managements have transient benefits with more than 90 recurrence rate within a year. Therefore, there is a significant unmet medical need. The purpose of this study is to assess the safety and efficacy of Trametinib in children and adults with Extracranial Arteriovenous Malformation (AVM).
Phase II Clinical Trial of MEK Inhibitor Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation (VM)
- Patient must be ≥ 12 years and ≤ 60 years
- Confirmed diagnosis of complicated extracranial AVMs made by a physician who is
familiar with this condition.
- Genetic testing for mutations within MAP2K1 or remaining RAS/MAPK pathway is preferred
but not mandatory
- Patient is able to swallow and/or retain oral medication via G tube
- All clinical and laboratory studies to determine eligibility will be performed within
six weeks prior to enrollment unless otherwise indicated.
- Patients who have undergone surgical resection or interventional radiology procedures
(sclerotherapy) of their AVM are eligible if they meet all inclusion criteria after
- At least 4 weeks from undergoing any major surgery
- Patients with endocrine deficiencies are allowed to receive physiologic or stress
doses of steroids if necessary.
- Myelosuppressive chemotherapy: None within 4 weeks of entry into this study.
- At least 14 days since the completion of therapy with a biologic. For agents that have
known adverse events occurring beyond 14 days after administration, this period must
be extended beyond the time during which adverse events are known to occur. These
patients must be discussed among PI and other investigators on a case-by-case basis.
- Patients must not have received an investigational drug within the prior 4 weeks.
- Not within 6 months prior to entering study if AVM is within field of radiation
- AVM due to germline mutation such as PTEN
- Prior MEK inhibitor therapy or have allergy or contraindication to MEK inhibitor
- Unable to swallow PO drugs or administer the drug via G tube
- Patients who have undergone major surgery ≤ 4 weeks prior to starting study treatment
or who have not recovered from side effects of such procedure
- Patients with evidence of or history of cardiovascular risk
- Patients with retinal vein occlusion, hemorrhage or have a history of such conditions.
- Patients who are currently on other immunosuppressive medication(s)
- Patients who have an uncontrolled infection
- Unstable health status that may interfere with completing study
- Unable to travel to clinic as requested
- Patients unwilling or unable to comply with the protocol, or who in the opinion of the
investigator may not be able to comply with the safety monitoring requirements of the
- Females of child-bearing potential must be willing to practice acceptable methods of
- Additionally, females of childbearing potential must have a negative serum pregnancy
test result from 7 days prior to the initiation of the medication to 3 months after
the final administration of the medication. Males or females of reproductive potential
may not participate unless they have agreed to use an effective contraceptive method
during the period when they are receiving the study drug and for 3 months thereafter.
drug: Trametinib tablet