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AzTrials

Venous MalformationPhase 2NCT04258046

Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation

A Phase 2 study testing Trametinib tablet in people with Venous Malformation and Arterial Disease, run by Stanford University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 12 to 60 years
Conditions the study is for
Venous Malformation, Arterial Disease
What is being tested?
Trametinib tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
1 Dec 2020to 18 Feb 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Pediatric Dermatology Clinic at Stanford Children's Hospital

    Palo Alto, California, 94304

Other trials in United States

About this study

Official title: Phase II Clinical Trial of MEK Inhibitor Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation (VM)

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).

Being tested
Trametinib tablet

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trametinib tabletDrug

    Drug is supplied in 0.5 mg and 2 mg tablets

Study groups in NCT04258046
Study groupRoleWhat they receive
Oral TrametinibExperimentalPatients will receive oral trametinib once daily
Receives: Drug: Trametinib tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease response rate by investigator assessment at Month 6

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

    Measured: Month 6

Secondary outcomes (3)

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

    Measured: Month 6

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

    Measured: 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.

    Measured: Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2020
  2. Study start1 Dec 2020
  3. Primary completion2 Feb 2026
  4. Study completion18 Feb 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04258046
Sponsor's protocol ID
53105
Status last verified
Apr 2026
First submitted
16 Jan 2020
Last updated
24 Apr 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trametinib tablet in people with Venous Malformation and Arterial Disease, run by Stanford University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease response rate by investigator assessment at Month 6 (time frame: Month 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04258046, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2026.

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