Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care

NCT02638389 | Recruiting Phase 3 DMC

• 1 other identifier: VASE
• Study Type: interventional
• Target: 250
• Locations: 3 countries
• Sites: 3

Brief Summary

The phosphatidylinositol 3-kinase (PI3Kinase)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTor) pathway plays a role on the development and the venous/lymphatic vascular organisations. The investigators want to study the efficacy and the safety of Rapamycin, an mTor inhibitor.

Conditions

Vascular Malformations

Outcome Measures

Primary Outcomes (1)

• Self-assesment (or parent assesment), using visual anagogic scale (0-10) of efficacy of sirolimus

  * Global treatment efficacy * Pain * Local complications/symptoms (bleeding, skin tension, esthetic and functional impairment)

  every 3 months, up to 2-year period.

Secondary Outcomes (5)

• Number of enrolled patients with treatment-related adverse events as assessed by CTCAE v4.0

  every month during the first three months and then every three months for a 2-year-treatment period

• Self assessment of quality of life change induced by sirolimus

  every 3 months, up to 2-year period.

• Volumetric changes of the malformation on sirolimus, based on magnetic resonance imaging (MRI) 12 months after sirolimus onset.

  At 12 month

• Efficacy of sirolimus

  every three months, up to 2-year period

• Efficacy of sirolimus measured on digital photographs

  every three months, up to 2-year period

Study Arms (1)

Patients with vascular malformations

EXPERIMENTAL

Patients with venous, lympathic or complex vascular malformations (KTS, PTEN, etc.) will receive sirolimus after completion of inclusion criteria

Drug: Sirolimus

Interventions

Sirolimus DRUG

evaluate the efficacy and safety of sirolimus in these patients

Also known as: Rapamycine

Patients with vascular malformations

Eligibility Criteria

• Age: 3 Months - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with complex vascular anomalies that are refractory to standard care such as medical treatment, surgical resection and/or sclerotherapy/embolization (ineffective or accompanied by major complications)
• Patients must have adequate medullary function: Hemoglobine\> 10,0 g/dl, neutrophils \>1500/mm³ and platelets \> 100.000/mm³
• Patients must have the following laboratory values:
• Total serum bilirubin ≤ 1.5 x ULN (or totally bilirubin ≤ 3 x ULN with direct bilirubin ≤ 1.5 x ULN in patients with well documented Gilbert Syndrome)
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (or \< 5.0 x ULN if hepatic metastases are present)
• Serum creatinine 1.5 x ULN. If the serum creatinine is ≥ 1.5 x ULN, then a 24-hour Creatinine Clearance must be conducted and the result must be ≥ 60 mL/min.
• Karnofsky \> 50
• Patients have to be able to sign the informed consent
• Women in age of procreation have to be informed that contraceptive methods are mandatory during the study time

You may not qualify if:

• Any of the following concurrent severe and/or uncontrolled medical conditions, which could compromise participation in the study or interfere with the study results:
• Impaired cardiac function or clinically significant cardiac diseases, including unstable angina pectoris, ventricular arrhythmia, valvular disease with documented compromise in cardiac function, myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function, history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy, family history of congenital long or short QT, or known history of QT/QTc prolongation of Torsades de Pointes (TdP)
• Impairment of Gastro-Intestinal (GI) function or GI disease that may significantly alter the absorption of sirolimus (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea ≥ Grade 2, malabsorption syndrome, or small bowel resection)
• Known hypersensitivity to drugs or metabolites from similar classes as study treatment.
• Patient has other concurrent severe and /or uncontrolled medical condition that would,in the investigator's judgment, contraindicated participation in the clinical study (e.g. acute or chronic pancreatitis, liver cirrhosis, active chronic hepatitis, severely impaired lung function with a spirometry ≤ 50% of the normal predicted value and/or O2 saturation ≤ 88% at rest, etc.)
• Immunocompromised patients, including known seropositivity for HIV
• Pregnant or lactating women
• Prior treatment with PI3K and/or mTOR inhibitors

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead

Study Sites (3)

Cliniques Universitaires Saint-Luc, Université Catholique de Louvain Bruxelles

Brussels, Brussels Capital, 1200, Belgium

RECRUITING

CHU Caen

Caen, Brittany Region, 14000, France

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

NOT YET RECRUITING

Related Publications (2)

• Seront E, Damme AV, Coulie J, Vikkula M, Boon LM. Personalized sirolimus regimen for vascular malformations: a retrospective analysis of VASE cohort. Orphanet J Rare Dis. 2025 Dec 10. doi: 10.1186/s13023-025-04151-y. Online ahead of print.

  PMID: 41366677 DERIVED

• Seront E, Van Damme A, Legrand C, Bisdorff-Bresson A, Orcel P, Funck-Brentano T, Sevestre MA, Dompmartin A, Quere I, Brouillard P, Revencu N, De Bortoli M, Hammer F, Clapuyt P, Dumitriu D, Vikkula M, Boon LM. Preliminary results of the European multicentric phase III trial regarding sirolimus in slow-flow vascular malformations. JCI Insight. 2023 Nov 8;8(21):e173095. doi: 10.1172/jci.insight.173095.

  PMID: 37937645 DERIVED

MeSH Terms

Conditions

Vascular Malformations

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Laurence M Boon, MD, PhD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurence M. Boon, MD, PhD

CONTACT

+ 32-2-764 8020; laurence.boon@uclouvain.be

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 23, 2015
• Study Start: January 25, 2016
• Primary Completion: April 1, 2025
• Study Completion (Estimated): April 1, 2030
• Last Updated: February 24, 2023

Record last verified: 2023-02

Locations

FR (1); DE (1); BE (1)