24VA022; VATCH Alpelisib for TIE2/PIK3CA Pathway VAs

NCT07543822 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB 24-022960GRT-00005474
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The study will enroll participants 2 months of age up to 30 years of age. The purpose of this study is to assess the effectiveness and safety of Alpelisib (the "Study Drug") in patients with PIK3CA/TIE-2/TEK pathway driven vascular anomalies (VA). Alpelisib has been approved by the U.S. Food and Drug Administration (FDA) for treating adults and children with certain types of breast cancer. Its use in this study is considered experimental because FDA has not approved the study drug for treating people with VAs. Study participation will last for up to 3 years and will involve regular study visits to Children's Hospital of Philadelphia (CHOP)'s Philadelphia Campus. Participants will need to take the study drug Alpelisib 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 for the purposes of the study. 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.

Conditions

Vascular Anomalies; Vascular Anomaly; TIE2/PIK3CA Pathway Driven Vascular Anomalies

Keywords

vascular anomalies; complex vascular anomalies; CaNVAS; PIK3CA; TIE-2/TEK; PIK3CA inhibitor; alpelisib

Outcome Measures

Primary Outcomes (3)

• Percentage of subjects with a Substantial Response or Intermediate Response to Alpelisib 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.

  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 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 and applied to the Individualized Response Criteria using the PROMIS global health T-scores.

  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.

Study Arms (1)

Main Study

EXPERIMENTAL

This arm will determine the proportion of subjects with an objective beneficial response to alpelisib 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 PIK3CA/TIE-2/TEK pathway driven vascular anomalies through various laboratory testing and clinical observations.

Drug: alpelisib (BYL719)

Interventions

alpelisib (BYL719) DRUG

Subjects will receive oral alpelisib daily in continuous 28-day cycles. Patients aged 18 years and older will start at 125 mg/day with a maximum dose of 250 mg/day; patients aged 6 - 17 years will start at 50 mg/day with a maximum dose of 200 mg/day. 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.

Also known as: vijoice, BYL719

Main Study

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed informed consent and assent (when applicable)
• Males or females age ≥ 2 years to \<=30 years at the time of informed consent.
• Have a documented PIK3CA or somatic TIE2/TEK 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.
• 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 that have received alpelisib previously either via Managed Access Program from Novartis or commercial supply are eligible to enroll IF they have been off alpelisib for at least 7 days and there is clinical progression/worsening while off treatment

You may not qualify if:

• Subject with only epidermal nevus/nevi in the absence of other PIK3CA vascular anomaly/overgrowth
• 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.
• Prior medications that are not allowable per the study protocol
• Participation in any other prior investigational study within 4 weeks prior to study treatment start and within 5 half-lives of the investigational product, whichever is longer
• Supportive care use of anticoagulants and compression garments is allowed. Subjects must have been using these interventions in an unchanged manner for 30 days before study enrollment.
• History of prior and or ongoing malignancy, or ongoing investigations or treatment for malignancy at time of informed consent.
• Clinically significant heart disease not due to VA
• Documented pneumonitis or interstitial lung disease not due to VA
• History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis
• Subjects with an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus
• Impaired gastrointestinal (GI) function that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• History of hypersensitivity to any drugs or metabolites of PI3K inhibitor or any of the excipients of alpelisib
• Known history of Steven Johnson's syndrome, erythema multiform or toxic epidermal necrolysis

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Novartis: collaborator
• CaNVAS (Consortium of Investigators of Vascular Anomalies): collaborator
• Texas Children's: collaborator
• Arkansas Children's Hospital Research Institute: collaborator
• Nationwide Children's Hospital: collaborator
• Nemours Children's Health: collaborator
• Boston Children's Hospital: collaborator
• NYU Langone Health: collaborator
• Children's Healthcare of Atlanta: collaborator
• Oregon Health and Science University: collaborator
• Children's Hospital Colorado: collaborator
• Riley Children's Health: collaborator
• Children's Hospital of Los Angeles (CHLA): collaborator
• Seattle Children's Hospital: collaborator
• Children's Hospital of Orange County (CHOC): collaborator
• Children's Wisconsin - Milwaukee: collaborator
• University of North Carolina: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• University of California, San Francisco: collaborator
• Children's Hospital of Pittsburg: collaborator
• Dell Children's Medical Center of Central Texas: collaborator
• Vanderbilt University Medical Center: collaborator
• Helen DeVos Children's Hospital: collaborator
• Washington University School of Medicine: collaborator
• Columbia University Irving Medical Center, New York, NY: collaborator
• Lucile Packard Children's Hospital Stanford: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Comprehensive Vascular Anomalies Program (CVAP) at CHOP
• CaNVAS Research Consortium

MeSH Terms

Conditions

Vascular Malformations; Hereditary Sensory and Autonomic Neuropathies

Interventions

Alpelisib

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2026
• First Posted: April 22, 2026
• Study Start: August 27, 2025
• Primary Completion (Estimated): August 27, 2029
• Study Completion (Estimated): August 27, 2030
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)