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Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04258046
Recruitment Status : Recruiting
First Posted : February 6, 2020
Last Update Posted : March 14, 2022
Sponsor:
Collaborator:
Boston Children's Hospital
Information provided by (Responsible Party):
Joyce Teng, Stanford University

Study Description
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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).

Condition or disease Intervention/treatment Phase
Venous Malformation Arterial Disease Drug: Trametinib tablet Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial of MEK Inhibitor Trametinib in the Treatment of Complicated Extracranial Arterial Venous Malformation (VM)
Actual Study Start Date : December 1, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Trametinib

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area [ Time Frame: Month 6 ]
  2. Change from baseline in MRI Volumetric Scan Measurement of Targeted Disease Area [ Time Frame: Month 12 ]
  3. 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.


Eligibility Criteria
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Ages Eligible for Study:   12 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04258046


Locations
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United States, California
Pediatric Dermatology Clinic at Stanford Children's Hospital Recruiting
Palo Alto, California, United States, 94304
Contact: Karima Belhocine    650-723-0636    PediatricDermStudy@stanford.edu   
Contact: Elidia V Tafoya, MPH       PediatricDermStudy@stanford.edu   
Principal Investigator: Joyce M Teng, MD, PhD         
Sponsors and Collaborators
Stanford University
Boston Children's Hospital
Investigators
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Principal Investigator: Joyce Teng, MD, PhD, FAAD Stanford University
More Information
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Publications:

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Responsible Party: Joyce Teng, Director of Pediatric Dermatology, Stanford University
ClinicalTrials.gov Identifier: NCT04258046    
Other Study ID Numbers: 53105
First Posted: February 6, 2020    Key Record Dates
Last Update Posted: March 14, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Congenital Abnormalities
Trametinib
Antineoplastic Agents
 Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action