Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation

NCT04258046 | Completed Phase 2 FDA Drug

• 1 other identifier: 53105
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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).

Conditions

Venous Malformation; Arterial Disease

Outcome Measures

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.

  Month 6

Secondary Outcomes (3)

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

  Month 6

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

  Month 12

• Disease response rate by investigator assessment at Month 12

  Month 12

Study Arms (1)

Oral Trametinib

EXPERIMENTAL

Patients will receive oral trametinib once daily

Drug: Trametinib tablet

Interventions

Trametinib tablet DRUG

Drug is supplied in 0.5 mg and 2 mg tablets

Oral Trametinib

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead
• Boston Children's Hospital: collaborator

Study Sites (1)

Pediatric Dermatology Clinic at Stanford Children's Hospital

Palo Alto, California, 94304, United States

Location

Related Publications (10)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Wright CJ, McCormack PL. Trametinib: first global approval. Drugs. 2013 Jul;73(11):1245-54. doi: 10.1007/s40265-013-0096-1.

  PMID: 23846731 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Interventions

trametinib

Study Officials

• Joyce Teng, MD, PhD, FAAD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Pediatric Dermatology

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: February 6, 2020
• Study Start: December 1, 2020
• Primary Completion: February 2, 2026
• Study Completion: February 18, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)