Ras/MAPK Pathway Vascular AnomaliesPhase 2VATCHNCT07549646
24VA021; VATCH Trametinib for Ras/MAPK Pathway VAs
A Phase 2 study testing Trametinib in people with Ras/MAPK Pathway Vascular Anomalies and Vascular Anomalies, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
The purpose of this study is to assess the effectiveness and safety of Trametinib (the "Study Drug") in patients with Ras/MAPK pathway driven vascular anomalies (VA). Trametinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma. Read more about this study
- Who is it for?
- Ages 2 months to 30 years
- Conditions the study is for
- Ras/MAPK Pathway Vascular Anomalies, Vascular Anomalies, Vascular Anomaly
- What is being tested?
- Trametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Aug 2025to 27 Oct 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 months to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Signed informed consent and assent (when applicable)
- Males or females age > 2 months to < 30 years at the time of informed consent.
- Have a documented Ras/MAPK-pathway variant.
- Have a symptomatic vascular anomaly in need of medical therapy.
- Have a disease-related lesion or lesions which can be measured
- Have a Lansky or Karnofsky performance status score of ≥ 50.
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- Have acceptable organ function
- (For persons who can get pregnant) Have a negative serum or urine pregnancy test within 7 days prior to starting study medication.
- Must agree to the use an acceptable method of contraception
- Subjects must be able to swallow tablets or liquid or use a nasogastric or gastric tube
Who cannot join
- Subjects seeking treatment for hypertrophic cardiomyopathy without a vascular anomaly
- Prior medications that are not allowable per the study protocol
- Confirmed or possible infections
- History of hepatic sinusoidal obstructive syndrome (veno-occlusive disease of the liver) in the last 3 months.
- Active gastrointestinal (GI) disease
- Subjects with history of or current risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) or uncontrolled glaucoma or ocular hypertension.
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- Allergic reactions: Subjects with a history of allergic reaction attributed to compounds of similar chemical or biological composition to trametinib are not eligible.
- History of prior and or ongoing cancer or ongoing investigations or treatment for cancer at time of informed consent.
- Subjects unable to comply with safety monitoring requirements.
- Subject may not be pregnant or breast feeding.
- Parents/guardian/LAR or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
- Debulking or other major surgery performed within 30 days, at time of informed consent;
- Clinically meaningful bleeding related to VA: Grade 2 within 14 days or Grade 3 and more within 28 days before study treatment start as per CTCAE v. 5.0.
- Sclerotherapy/embolization for vascular complications performed within 14 days before informed consent.
- Subjects not able to understand and to comply with study instructions and requirements (in patients, legally authorized representatives, or guardians as applicable) at time of informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
CVAP Research Team, CVAPResearch@chop.edu
Denise M Adams, MD
About this study
Official title: VATCH (Vascular Anomaly Analysis for Therapy Choice): A Phase II Study of Trametinib Treatment in Subjects With Ras/MAPK Pathway Driven Vascular Anomalies
The purpose of this study is to assess the effectiveness and safety of Trametinib (the "Study Drug") in patients with Ras/MAPK pathway driven vascular anomalies (VA). Trametinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma. Its use in this study is considered experimental because the FDA has not approved the study drug for treating people with VAs.
The study will enroll participants 2 months of age up to 30 years of age that have been diagnosed with Ras/MAPK pathway driven vascular anomalies.
Study participation will last up to 3 years and will involve regular study visits to Children's Hospital of Philadelphia (CHOP) Philadelphia Campus. Participants will need to take the study drug Trametinib for at least 2 years, or up to 3 years in total, if there is a positive response. Participating in this research means you will attend up to 16 clinic visits. Most visits will take approximately 30 minutes, but some visits will take approximately 2 hours, because you will be asked to complete questionnaires about your experience. Participating in this research also means taking the study drug, having pictures taken, and completing study drug diaries. There is also an optional portion to this study that involves collecting blood for biomarker testing.
- Being tested
- Trametinib
- Keywords
- trametinib, vascular anomalies, complex vascular anomalies, Ras/MAPK pathway, CaNVAS, MEK inhibitor
- Medical subject headings
- Vascular Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrametinibDrug
Also called TMT212, GSK1120212
Subjects will receive oral trametinib daily in continuous 28-day cycles at 0.025 mg/kg/day with a maximum dose of 2 mg. A single dose reduction will be permitted in individual subjects who experience toxicity while still having evidence of clinical benefit and is assessed per the investigator.
| Study group | Role | What they receive |
|---|---|---|
| Main Study | Experimental | This arm will determine the proportion of subjects with an objective beneficial response to trametinib at the end of cycle 6 using an individualized response criterion based on radiologic assessment, Patient Reported Outcomes (PROs) and Clinical Benefit Assessment (CBA). It will also determine the safety of oral trametinib in children and young adults with Ras/MAPK pathway driven vascular anomalies through various laboratory testing and clinical observations. Receives: Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of subjects with a Substantial Response or Intermediate Response to Trametinib using an Individualized Response Criteria
Individualized Response is a composite outcome determined by the combined results of the following 3 distinct study assessments after cycle 6: Radiologic evaluation, PROMIS Patient reported outcome (PRO) measurements, and Clinical Benefit Assessments (CBA). The results of these 3 distinct assessments will be evaluated using a set of specific criteria to determine the Individualized Response to treatment (i.e. "Substantial Response" = Improvement in Radiologic assessment by 20%, AND improvement in Global Health PROs by 3T-score points, AND improvement in at least 1 CBA, AND no clinically meaningful worsening of disease).
Each subject will be determined to have: 1) Substantial Response, or 2) Intermediate Response, or 3) Stable disease, or 4) Worsening disease. A subject that is found to have a Substantial Response or Intermediate Response is considered to have a "beneficial response." Statistical analyses will be run to determine the percentage of subjects with a beneficial response.
Measured: Individualized Response Criteria will be evaluated after 6 cycles (each cycle is 28 days) and then every 6 months until the end of the study (approximately 1.5 years)
Relative size of target lesion(s) as determined by radiologic assessment
For subjects with radiologically evaluable disease only The target lesion(s) will be measured at screening using imaging modality of choice based on underlying vascular anomaly (e.g. Magnetic Resonance Imaging (MRI), Magnetic Resonance Lymphangiography (MRL), US, X-rays, CT scan). MRI or MRL imaging will be recommended as primary imaging modality. For subjects with disease manifestation better characterized by alternative quantitative imaging modality (e.g. X-ray or ultrasound) this may be substituted and used as alternative imaging. Up to 3 lesions will be identified as target lesions and recorded and measured at screening. The same method of assessment and the same technique will be used to characterize each target lesion at the specified follow-up timepoints. CBA can be substituted for radiologic evaluation in subjects without radiologically evaluable disease.
Measured: Measured at screening and after cycles 6, 12, and 24. Each cycle is 28 days.
Quality of life as evaluated by PROMIS Patient Reported Outcome (PRO) questionnaire T-scores
Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires will be distributed to subjects and caregivers (if applicable.) A raw score will be calculated for each PROMIS subscale. Raw scores will then be translated into a T-score metric with mean of 50 (standard deviation of 10). A higher T-score means more of the outcome being measured. Global health measures will be used as the primary outcome. Change in quality of life will be evaluated \& applied to the Individualized Response Criteria using the PROMIS global health T-scores.
Measured: Begin at screening and after cycles 6, 12, and 24. If subject enters extension phase, will continue to measure every 6 cycles until end of therapy (approximately 1 year). Each cycle is 28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2026
- Study start27 Aug 2025
- Primary completion27 Oct 2029 (estimated)
- Study completion27 Oct 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ras/MAPK Pathway Vascular AnomaliesStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- This is a Phase II multi-center non-randomized study to assess the safety and efficacy of trametinib with Ras/MAPK pathway driven vascular anomalies.
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, CaNVAS (Consortium of Investigators of Vascular Anomalies), Baylor College of Medicine, Arkansas Children's Hospital Research Institute, Nationwide Children's Hospital, Nemours Children's Health, Boston Children's Hospital, NYU Langone Health, Children's Healthcare of Atlanta, Oregon Health and Science University, Children's Hospital Colorado, Riley Children's Health, Children's Hospital of Los Angeles (CHLA), Seattle Children's Hospital, Children's Hospital of Orange County, Children's Wisconsin - Milwaukee, University of North Carolina, Children's Hospital Medical Center, Cincinnati, University of California, San Francisco, Columbia University, Children's Hospital of Pittsburg, Dell Children's Medical Center of Central Texas, Vanderbilt University Medical Center, Helen DeVos Children's Hospital, Washington University School of Medicine, Lucile Packard Children's Hospital Stanford
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07549646
- Sponsor's protocol ID
- IRB 24-022959
- Other IDs
- GRT-00005473
- Acronym
- VATCH
- Status last verified
- Oct 2026
- First submitted
- 20 Jan 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VATCH (Vascular Anomaly Analysis for Therapy Choice): A Phase II Study of Trametinib Treatment in Subjects With Ras/MAPK Pathway Driven Vascular Anomalies
- ClinicalTrials.gov ID
- NCT07549646
- Acronym / sponsor ID
- VATCH / IRB 24-022959
- Keywords
- trametinib, vascular anomalies, complex vascular anomalies, Ras/MAPK pathway, CaNVAS, MEK inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Novartis, CaNVAS (Consortium of Investigators of Vascular Anomalies), Baylor College of Medicine, Arkansas Children's Hospital Research Institute, Nationwide Children's Hospital, Nemours Children's Health, Boston Children's Hospital, NYU Langone Health, Children's Healthcare of Atlanta, Oregon Health and Science University, Children's Hospital Colorado, Riley Children's Health, Children's Hospital of Los Angeles (CHLA), Seattle Children's Hospital, Children's Hospital of Orange County, Children's Wisconsin - Milwaukee, University of North Carolina, Children's Hospital Medical Center, Cincinnati, University of California, San Francisco, Columbia University, Children's Hospital of Pittsburg, Dell Children's Medical Center of Central Texas, Vanderbilt University Medical Center, Helen DeVos Children's Hospital, Washington University School of Medicine, Lucile Packard Children's Hospital Stanford
- Study start
- 27 Aug 2025 (actual)
- Primary completion
- 27 Oct 2029 (estimated)
- Study completion
- 27 Oct 2030 (estimated)
- First posted
- 24 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the effectiveness and safety of Trametinib (the "Study Drug") in patients with Ras/MAPK pathway driven vascular anomalies (VA). Trametinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma. Its use in this study is considered experimental because the FDA has not approved the study drug for treating people with VAs.
The study will enroll participants 2 months of age up to 30 years of age that have been diagnosed with Ras/MAPK pathway driven vascular anomalies.
Study participation will last up to 3 years and will involve regular study visits to Children's Hospital of Philadelphia (CHOP) Philadelphia Campus. Participants will need to take the study drug Trametinib for at least 2 years, or up to 3 years in total, if there is a positive response. Participating in this research means you will attend up to 16 clinic visits. Most visits will take approximately 30 minutes, but some visits will take approximately 2 hours, because you will be asked to complete questionnaires about your experience. Participating in this research also means taking the study drug, having pictures taken, and completing study drug diaries. There is also an optional portion to this study that involves collecting blood for biomarker testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a Phase II multi-center non-randomized study to assess the safety and efficacy of trametinib with Ras/MAPK pathway driven vascular anomalies.
| Arm | Type | Receives |
|---|---|---|
| Main Study | Experimental | Drug: TrametinibThis arm will determine the proportion of subjects with an objective beneficial response to trametinib at the end of cycle 6 using an individualized response criterion based on radiologic assessment, Patient Reported Outcomes (PROs) and Clinical Benefit Assessment (CBA). It will also determine the safety of oral trametinib in children and young adults with Ras/MAPK pathway driven vascular anomalies through various laboratory testing and clinical observations. |
Who may qualify
- Ages
- 2 months to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Signed informed consent and assent (when applicable)
- Males or females age > 2 months to < 30 years at the time of informed consent.
- Have a documented Ras/MAPK-pathway variant.
- Have a symptomatic vascular anomaly in need of medical therapy.
- Have a disease-related lesion or lesions which can be measured
Key exclusion criteria (15 listed)
- Subjects seeking treatment for hypertrophic cardiomyopathy without a vascular anomaly
- Prior medications that are not allowable per the study protocol
- Confirmed or possible infections
- History of hepatic sinusoidal obstructive syndrome (veno-occlusive disease of the liver) in the last 3 months.
- Active gastrointestinal (GI) disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrametinibAlso: TMT212, GSK1120212Subjects will receive oral trametinib daily in continuous 28-day cycles at 0.025 mg/kg/day with a maximum dose of 2 mg. A single dose reduction will be permitted in individual subjects who experience toxicity while still having evidence of clinical benefit and is assessed per the investigator. | Drug | Main Study |
Primary outcome
Percentage of subjects with a Substantial Response or Intermediate Response to Trametinib using an Individualized Response Criteria
Time frame: Individualized Response Criteria will be evaluated after 6 cycles (each cycle is 28 days) and then every 6 months until the end of the study (approximately 1.5 years)
Individualized Response is a composite outcome determined by the combined results of the following 3 distinct study assessments after cycle 6: Radiologic evaluation, PROMIS Patient reported outcome (PRO) measurements, and Clinical Benefit Assessments (CBA). The results of these 3 distinct assessments will be evaluated using a set of specific criteria to determine the Individualized Response to treatment (i.e. "Substantial Response" = Improvement in Radiologic assessment by 20%, AND improvement in Global Health PROs by 3T-score points, AND improvement in at least 1 CBA, AND no clinically meaningful worsening of disease). Each subject will be determined to have: 1) Substantial Response, or 2) Intermediate Response, or 3) Stable disease, or 4) Worsening disease. A subject that is found to have a Substantial Response or Intermediate Response is considered to have a "beneficial response." Statistical analyses will be run to determine the percentage of subjects with a beneficial response.
Relative size of target lesion(s) as determined by radiologic assessment
Time frame: Measured at screening and after cycles 6, 12, and 24. Each cycle is 28 days.
For subjects with radiologically evaluable disease only The target lesion(s) will be measured at screening using imaging modality of choice based on underlying vascular anomaly (e.g. Magnetic Resonance Imaging (MRI), Magnetic Resonance Lymphangiography (MRL), US, X-rays, CT scan). MRI or MRL imaging will be recommended as primary imaging modality. For subjects with disease manifestation better characterized by alternative quantitative imaging modality (e.g. X-ray or ultrasound) this may be substituted and used as alternative imaging. Up to 3 lesions will be identified as target lesions and recorded and measured at screening. The same method of assessment and the same technique will be used to characterize each target lesion at the specified follow-up timepoints. CBA can be substituted for radiologic evaluation in subjects without radiologically evaluable disease.
Quality of life as evaluated by PROMIS Patient Reported Outcome (PRO) questionnaire T-scores
Time frame: Begin at screening and after cycles 6, 12, and 24. If subject enters extension phase, will continue to measure every 6 cycles until end of therapy (approximately 1 year). Each cycle is 28 days.
Patient Reported Outcomes Measurement Information System (PROMIS) questionnaires will be distributed to subjects and caregivers (if applicable.) A raw score will be calculated for each PROMIS subscale. Raw scores will then be translated into a T-score metric with mean of 50 (standard deviation of 10). A higher T-score means more of the outcome being measured. Global health measures will be used as the primary outcome. Change in quality of life will be evaluated \& applied to the Individualized Response Criteria using the PROMIS global health T-scores.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Comprehensive Vascular Anomalies Program (CVAP) at CHOPLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trametinib in people with Ras/MAPK Pathway Vascular Anomalies and Vascular Anomalies, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact CVAP Research Team (267-426-9188, CVAPResearch@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of subjects with a Substantial Response or Intermediate Response to Trametinib using an Individualized Response Criteria (time frame: Individualized Response Criteria will be evaluated after 6 cycles (each cycle is 28 days) and then every 6 months until the end of the study (approximately 1.5 years)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.