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NCT04258046 · CITED IN SOURCE DOCUMENTS

Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2026-04-24

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
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: * 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.
healthy Volunteers
false
maximum Age
60 Years
minimum Age
12 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients will receive oral trametinib once daily
    intervention Names
    1. Drug: Trametinib tablet
    label
    Oral Trametinib
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Oral Trametinib
    description
    Drug is supplied in 0.5 mg and 2 mg tablets
    name
    Trametinib tablet
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
25
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Combining a composite of radiographic, clinical, functional impairment, and quality of life measures.
    measure
    Disease response rate by investigator assessment at Month 6
    time Frame
    Month 6
secondary Outcomes
  1. measure
    Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area
    time Frame
    Month 6
  2. measure
    Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area
    time Frame
    Month 12
  3. description
    Combining a composite of radiographic, clinical, functional impairment, and quality of life measures.
    measure
    Disease response rate by investigator assessment at Month 12
    time Frame
    Month 12
Full study description
brief 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).
Source references
references
  1. citation
    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.
    pmid
    20335868
    type
    BACKGROUND
  2. citation
    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.
    pmid
    28190454
    type
    BACKGROUND
  3. citation
    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.
    pmid
    31486960
    type
    BACKGROUND
  4. citation
    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.
    pmid
    30069762
    type
    BACKGROUND
  5. citation
    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.
    pmid
    30465279
    type
    BACKGROUND
  6. citation
    Wright CJ, McCormack PL. Trametinib: first global approval. Drugs. 2013 Jul;73(11):1245-54. doi: 10.1007/s40265-013-0096-1.
    pmid
    23846731
    type
    BACKGROUND
  7. citation
    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.
    pmid
    23413975
    type
    BACKGROUND
  8. citation
    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.
    pmid
    30566190
    type
    BACKGROUND
  9. citation
    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.
    pmid
    26783326
    type
    BACKGROUND
  10. citation
    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.
    pmid
    28955111
    type
    BACKGROUND
  11. citation
    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.
    pmid
    40148035
    type
    DERIVED
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        display
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    Preserved source evidence · Not medical advice