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CompletedNCT04258046Updated Apr 24, 2026

Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation

A Phase 2 interventional study of Trametinib tablet in Venous Malformation and Arterial Disease, sponsored by Stanford University. Completed at 1 site in United States. Open to participants aged 12 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-04-24.

Sponsored by Stanford University · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
25
Allocation
Not applicable
Ages
12 Years to 60 Years
Sex
All
01

Study summary

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).

02

Conditions studied

  • Venous Malformation
  • Arterial Disease
03

In context

Lead sponsor

Stanford University is the lead sponsor of 2,117 studies on the registry; 425 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 197 (76%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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 these procedures
  • 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

Exclusion criteria

Exclusion Criteria:

  • 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 study.
  • Females of child-bearing potential must be willing to practice acceptable methods of birth control.
  • 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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    Oral Trametinib

    Patients will receive oral trametinib once daily

    Drug: Trametinib tablet

Interventions

  • DrugTrametinib tablet

    Drug is supplied in 0.5 mg and 2 mg tablets

06

What researchers measure

Primary outcomes

  1. Disease response rate by investigator assessment at Month 6

    Combining a composite of radiographic, clinical, functional impairment, and quality of life measures.

    Time frame: Month 6

Secondary outcomes

  1. Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area

    Time frame: Month 6

  2. Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area

    Time frame: Month 12

  3. Disease response rate by investigator assessment at Month 12

    Combining a composite of radiographic, clinical, functional impairment, and quality of life measures.

    Time frame: Month 12

07

Study locations

1 site
  • Pediatric Dermatology Clinic at Stanford Children's Hospital
    Palo Alto, California 94304, United States
08

References and documents

Publications

  • Liu AS, Mulliken JB, Zurakowski D, Fishman SJ, Greene AK. Extracranial arteriovenous malformations: natural progression and recurrence after treatment. Plast Reconstr Surg. 2010 Apr;125(4):1185-1194. doi: 10.1097/PRS.0b013e3181d18070. PubMed 20335868 ↗
  • Couto JA, Huang AY, Konczyk DJ, Goss JA, Fishman SJ, Mulliken JB, Warman ML, Greene AK. Somatic MAP2K1 Mutations Are Associated with Extracranial Arteriovenous Malformation. Am J Hum Genet. 2017 Mar 2;100(3):546-554. doi: 10.1016/j.ajhg.2017.01.018. Epub 2017 Feb 9. PubMed 28190454 ↗
  • Goss JA, Konczyk DJ, Smits PJ, Kozakewich HPW, Alomari AI, Al-Ibraheemi A, Taghinia AH, Dickie BH, Adams DM, Fishman SJ, Mulliken JB, Warman ML, Greene AK. Intramuscular fast-flow vascular anomaly contains somatic MAP2K1 and KRAS mutations. Angiogenesis. 2019 Nov;22(4):547-552. doi: 10.1007/s10456-019-09678-w. Epub 2019 Sep 5. PubMed 31486960 ↗
  • Zeiser R, Andrlova H, Meiss F. Trametinib (GSK1120212). Recent Results Cancer Res. 2018;211:91-100. doi: 10.1007/978-3-319-91442-8_7. PubMed 30069762 ↗
  • Hashemzadeh S, Ramezani F, Rafii-Tabar H. Study of Molecular Mechanism of the Interaction Between MEK1/2 and Trametinib with Docking and Molecular Dynamic Simulation. Interdiscip Sci. 2019 Mar;11(1):115-124. doi: 10.1007/s12539-018-0305-4. Epub 2018 Nov 21. PubMed 30465279 ↗
  • Wright CJ, McCormack PL. Trametinib: first global approval. Drugs. 2013 Jul;73(11):1245-54. doi: 10.1007/s40265-013-0096-1. PubMed 23846731 ↗
  • Green JS, Norris DA, Wisell J. Novel cutaneous effects of combination chemotherapy with BRAF and MEK inhibitors: a report of two cases. Br J Dermatol. 2013 Jul;169(1):172-6. doi: 10.1111/bjd.12279. PubMed 23413975 ↗
  • Lekwuttikarn R, Lim YH, Admani S, Choate KA, Teng JMC. Genotype-Guided Medical Treatment of an Arteriovenous Malformation in a Child. JAMA Dermatol. 2019 Feb 1;155(2):256-257. doi: 10.1001/jamadermatol.2018.4653. PubMed 30566190 ↗
  • Adams DM, Trenor CC 3rd, Hammill AM, Vinks AA, Patel MN, Chaudry G, Wentzel MS, Mobberley-Schuman PS, Campbell LM, Brookbank C, Gupta A, Chute C, Eile J, McKenna J, Merrow AC, Fei L, Hornung L, Seid M, Dasgupta AR, Dickie BH, Elluru RG, Lucky AW, Weiss B, Azizkhan RG. Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies. Pediatrics. 2016 Feb;137(2):e20153257. doi: 10.1542/peds.2015-3257. Epub 2016 Jan 18. PubMed 26783326 ↗
  • Steiner JE, Drolet BA. Classification of Vascular Anomalies: An Update. Semin Intervent Radiol. 2017 Sep;34(3):225-232. doi: 10.1055/s-0037-1604295. Epub 2017 Sep 11. PubMed 28955111 ↗
  • Avolio E, Bassani B, Campanile M, Mohammed KA, Muti P, Bruno A, Spinetti G, Madeddu P. Shared molecular, cellular, and environmental hallmarks in cardiovascular disease and cancer: Any place for drug repurposing? Pharmacol Rev. 2025 Mar;77(2):100033. doi: 10.1016/j.pharmr.2024.100033. Epub 2024 Dec 24. PubMed 40148035 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 24, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04258046
Lead sponsor
Stanford University
Collaborators
Boston Children's Hospital
Responsible party
Joyce Teng (Director of Pediatric Dermatology, Stanford University) — Principal investigator
First posted
Feb 6, 2020
Start date
Dec 1, 2020
Primary completion
Feb 2, 2026
Completion
Feb 18, 2026
Last update
Apr 24, 2026

Study contacts

Joyce Teng, MD, PhD, FAAD
principal investigator · Stanford University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.

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