Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation

NCT ID: NCT04258046

Last Updated: 2023-06-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-01

Study Completion Date

2024-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Venous Malformation Arterial Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Oral Trametinib

Patients will receive oral trametinib once daily

Group Type EXPERIMENTAL

Trametinib tablet

Intervention Type DRUG

Drug is supplied in 0.5 mg and 2 mg tablets

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Trametinib tablet

Drug is supplied in 0.5 mg and 2 mg tablets

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
* 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.
Minimum Eligible Age

12 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Boston Children's Hospital

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Joyce Teng

Director of Pediatric Dermatology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Joyce Teng, MD, PhD, FAAD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Pediatric Dermatology Clinic at Stanford Children's Hospital

Palo Alto, California, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Karima Belhocine

Role: primary

650-723-0636

Elidia V Tafoya, MPH

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 20335868 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28190454 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31486960 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30069762 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30465279 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 23846731 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23413975 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30566190 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26783326 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28955111 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

53105

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Study of MEK162 for Children With Low-Grade Gliomas
NCT02285439 COMPLETED PHASE1/PHASE2