Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation

June 9, 2023 updated by: Joyce Teng, Stanford University

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral Trametinib
Patients will receive oral trametinib once daily
Drug: Trametinib tablet
Drug is supplied in 0.5 mg and 2 mg tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease response rate by investigator assessment at Month 6
Time Frame: Month 6
Combining a composite of radiographic, clinical, functional impairment, and quality of life measures.
Month 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area
Time Frame: Month 6
Month 6
Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area
Time Frame: Month 12
Month 12
Disease response rate by investigator assessment at Month 12
Time Frame: Month 12
Combining a composite of radiographic, clinical, functional impairment, and quality of life measures.
Month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

Boston Children's Hospital

Investigators

  • Principal Investigator: Joyce Teng, MD, PhD, FAAD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2020

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

January 16, 2020

First Submitted That Met QC Criteria

February 4, 2020

First Posted (Actual)

February 6, 2020

Study Record Updates

Last Update Posted (Actual)

June 12, 2023

Last Update Submitted That Met QC Criteria

June 9, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 53105

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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