Trametinib for Vascular Anomalies

(VATCH Trial)

Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: Children's Hospital of Philadelphia
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of Trametinib, a drug already approved for treating melanoma, in individuals with certain vascular anomalies (unusual blood vessel growths) driven by the Ras/MAPK pathway. The goal is to determine if this drug can reduce the symptoms or size of these anomalies. Participants should have a symptomatic vascular anomaly and a known Ras/MAPK pathway variant.

As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant medical advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that prior medications that are not allowable per the study protocol could exclude you from participating, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that Trametinib is likely to be safe for humans?

Research has shown that Trametinib, a treatment being tested for blood vessel disorders, appears to be safe. The FDA has already approved this drug for treating metastatic melanoma, indicating it has undergone safety testing for that condition. In studies on blood vessel disorders, Trametinib was generally well-tolerated by patients.

For instance, one study found that 80% of patients showed improvement, and those experiencing pain felt much better. Another study demonstrated that Trametinib helped treat early-stage abnormal connections between arteries and veins over a year, with manageable side effects.

While these results are promising, Trametinib remains experimental for blood vessel disorders. Ongoing trials closely monitor its safety. Participants in these studies help researchers understand how well the treatment works across different ages and conditions.12345

Why do researchers think this study treatment might be promising?

Trametinib is unique because it targets the Ras/MAPK pathway, a key driver in certain vascular anomalies, which is not specifically targeted by most existing treatments. Current options often focus on symptom management rather than directly addressing the underlying molecular causes. Trametinib, as a MEK inhibitor, directly interferes with the signaling pathway responsible for the growth and maintenance of these anomalies. This targeted approach could offer more effective relief with potentially fewer side effects, making researchers hopeful for its ability to provide a more precise treatment option for patients.

What evidence suggests that Trametinib might be an effective treatment for vascular anomalies?

Research has shown that Trametinib may help treat certain blood vessel problems caused by issues in the Ras/MAPK pathway. Previous studies found that Trametinib, which blocks a specific protein, can significantly reduce these blood vessel issues. In one study, participants experienced more than a 50% improvement in skin problems after using Trametinib. Additionally, Trametinib has proven effective in helping people with complex lymphatic issues, another type of blood vessel condition. This trial will evaluate the effectiveness and safety of Trametinib in children and young adults with Ras/MAPK pathway-driven vascular anomalies, suggesting that Trametinib could be a useful option for managing these types of blood vessel problems.12467

Are You a Good Fit for This Trial?

This trial is for children and young adults (ages 2 months to under 30 years) with vascular anomalies caused by Ras/MAPK pathway changes, who have symptoms needing treatment. Participants must be able to take medicine by mouth or tube, have measurable lesions, good organ function, and agree to use birth control if needed.

Inclusion Criteria

1. Signed informed consent and assent (when applicable)
I have tumors or lesions that can be measured by scans or exams.
8. (For persons who can get pregnant) Have a negative serum or urine pregnancy test within 7 days prior to starting study medication.
See 7 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks
1 visit (in-person)

Treatment

Participants receive Trametinib for at least 2 years, with regular assessments every 6 cycles (each cycle is 28 days)

2-3 years
Up to 16 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 6 months

1.5 years

Extension

Optional extension phase for continued monitoring and treatment if beneficial response is observed

1 year

What Are the Treatments Tested in This Trial?

Interventions

  • Trametinib

Trial Overview

The study tests Trametinib, an FDA-approved cancer drug used here experimentally for vascular anomalies linked to the Ras/MAPK pathway. Participants will take Trametinib daily for at least 2 years (up to 3), with regular clinic visits over a total of up to 3 years.

How Is the Trial Designed?

1

Treatment groups

Experimental Treatment

Group I: Main StudyExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials
749
Recruited
11,400,000+

Arkansas Children's Hospital Research Institute

Collaborator

Trials
141
Recruited
5,025,000+

Nemours Children's Health

Collaborator

Trials
1
Recruited
5,000+

Boston Children's Hospital

Collaborator

Trials
801
Recruited
5,584,000+

NYU Langone Health

Collaborator

Trials
1,431
Recruited
838,000+

Children's Healthcare of Atlanta

Collaborator

Trials
172
Recruited
108,000+

Oregon Health and Science University

Collaborator

Trials
1,024
Recruited
7,420,000+

Riley Children's Health

Collaborator

Children's Hospital of Los Angeles (CHLA)

Collaborator

Trials
2
Recruited
3,600+

Children's Wisconsin - Milwaukee

Collaborator

Citations

24VA021; VATCH Trametinib for Ras/MAPK Pathway VAs

The purpose of this study is to assess the effectiveness and safety of Trametinib (the "Study Drug") in patients with Ras/MAPK pathway ...

MEK Inhibition Reduces Vascular Malformations and Gene ...

Trametinib was the most effective MEK inhibitor, correcting some dysregulated genes in NRASQ61R EC, including some in the Notch pathway.

Trametinib for Vascular Anomalies · Info for Participants

The purpose of this study is to assess the effectiveness and safety of Trametinib (the "Study Drug") in patients with Ras/MAPK pathway ...

Trametinib treatment for early-stage extracranial ...

In this study, we observed clinical improvement in all of the participants after trametinib, with an average blanching rate of skin lesions exceeding 50%, a ...

Inhibiting PI3K and MAPK Pathways

This case report highlights a patient with PHTS treated with sirolimus and trametinib as combined targeted therapy.

34: Updates of Targeted Therapies for Vascular Anomalies

MEK inhibitors like trametinib, for metastatic melanoma and non-small cell lung cancer, are now used for vascular anomalies targeting mutations of the RAS/MAPK ...

Targeted medical therapies for vascular anomalies - PMC - NIH

Several case reports have cited clinical improvement or stability with trametinib use in patients with AVMs who have not been responsive to ...