A Study of Clinical Practice and Real-world Care of Patients Treated With mTOR, PI3K, and MEK Inhibitors for Extracranial Vascular Anomalies

Targeted Therapies for Vascular Anomalies: A MultiCenter Real World Registry A Review of Clinical Practice and Real-world Care of Patients Treated With mTOR, PI3K, and MEK Inhibitors for Extracranial Vascular Anomalies

This study aims to describe real-world patient characteristics, treatment patterns, and adverse events associated with targeted therapies used in patients with complex vascular anomalies. The study will create an active registry for participating centers to enter data on patients with complex vascular anomalies being treated with sirolimus/everolimus (mTOR inhibitors), with/without trametinib (MEK inhibitor), or alpelisib (PIK3CA inhibitor). Tertiary care centers in the United States (US) that receive referrals for complex vascular anomaly cases and use Electronic Health Records (EHRs) will contribute patient medical chart reviews to this registry.

Study Overview

• Status: Not yet recruiting
• Conditions: Vascular Anomalies

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pediatric and adult patients with complex vascular anomalies who have been treated for at least three months with mTOR inhibitors, PI3K inhibitors, and/or MEK inhibitors at academic and community vascular centers across the US.

Description

Inclusion criteria:

• Diagnosed with a spectrum of vascular anomalies including but not limited to congenital vascular and lymphatic anomalies, vascular tumors and lymphatic malformations, and acquired vascular malformations.
• Treated with ≥1 of mammalian target of rapamycin (mTOR) inhibitors, mitogen-activated protein kinase/ERK kinase (MEK) inhibitors and phosphoinositide 3-kinase (PI3K) inhibitors continuously for 3 months.

Exclusion criteria:

• Patients diagnosed with a vascular anomaly who have not been treated with mTOR inhibitors, MEK inhibitors and PI3K inhibitors for at least 3 months.
• Patients with other complex medical conditions; i.e. rare genetic syndromes.
• Patients receiving many other systemic therapies making data collection not feasible.
• Recurrent use of immunosuppressive agents, i.e. systemic steroids or targeted medical therapies for oncologic disorders, etc.
• Patients with significant gaps in data collection.
• Patients with concurrent enrollment in interventional trials.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Complex Vascular Anomaly Group; Patients with vascular anomalies that were treated with mTOR inhibitors (sirolimus/everolimus), a MEK inhibitor (trametinib), and a PIK3CA inhibitor (alpelisib) for a minimum of 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Demographics		Baseline
Number of Patients by Clinical Characteristics	Characteristics include vascular anomaly diagnosis, family history of vascular anomalies, cancer diagnosis, disease severity and anatomic locations involved, associated complications, other medical and surgical interventions, and other medications used.	Baseline
Number of Patients by Treatment Received in Each Line of Therapy		Up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events per Person per Year (PPPY)		Up to 10 years
Total Number of Adverse Events		Up to 10 years
Percentage of Patients With Adverse Events		Up to 10 years
Number of Clinical Response Events PPPY	Clinical response: improvement of function, reduction of symptoms and complications, i.e. pain, infection, bleeding, hospitalization, etc.	Up to 10 years
Total Number of Clinical Response Events		Up to 10 years
Percentage of Patients Who Experience a Clinical Response		Up to 10 years
Treatment Duration		Up to 10 years
Number of Patients by Reason for Treatment Discontinuation		Up to 10 years
Frequency of Labs and Imaging for Disease Monitoring		Up to 10 years
Frequency of Adverse Events in Organ Systems		Up to 10 years
Percentage of Patients With Disease/Quality of Life (QoL) Impact	Since this is not a clinical trial and validated instruments are not frequently used in routine clinical visits, disease/QoL impact will be defined by impact on daily activities (walking ambulation, hobbies), demand on multidisciplinary care and impact on emotions (mood, self-esteem).	Up to 10 years
Percentage of Patients With Clinical Parameters Relevant to Routine Care	Clinical parameters will include dosing and treatment duration and frequency of follow up.	Up to 10 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): October 29, 2027
• Study Completion (Estimated): October 29, 2027

Study Registration Dates

• First Submitted: August 11, 2026
• First Submitted That Met QC Criteria: August 11, 2026
• First Posted (Actual): August 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 1, 2026
• Last Update Submitted That Met QC Criteria: August 31, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: QoL; Targeted therapy; MEK inhibitor; mTOR inhibitor; Vascular anomaly; Pi3KCA inhibitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Vascular Malformations
• Other Study ID Numbers: CBYL719F1US02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO