Vascular MalformationsPhase 3NCT02638389
Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care
A Phase 3 study testing Sirolimus in people with Vascular Malformations, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 3 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 months to 70 years
- Conditions the study is for
- Vascular Malformations
- What is being tested?
- Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 25 Jan 2016to 1 Apr 2030
- Phase
- Phase 3
- 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 3 months to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 3 countries
Belgium1 site, 1 recruiting
- Recruiting
Cliniques Universitaires Saint-Luc, Université Catholique de Louvain Bruxelles
Brussels, Brussels Capital, 1200
Laurence M Boon, MD, PhD, + 32-2-764 8020, laurence.boon@uclouvain.be
Emmanuel Seront, MD, PhD, + 32-2-764 1992, emmanuel.seront@uclouvain.be
France1 site, 1 recruiting
- Recruiting
CHU Caen
Caen, Brittany Region, 14000
Anne Dompmartin, MD, PhD, dompmartin-a@chu-caen.fr
Fabien Chaillot, chaillot-f@chu-caen.fr
Germany1 site, 1 recruiting
- Not yet recruiting
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Jochen Roessler, MD, PhD, jochen.roessler@uniklinik-freiburg.de
Jochen Roessler, MD, PhD
About this study
Official title: Phase III Multicentric Study Evaluating the Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care
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.
Read the detailed description
The complex vascular malformations induce chronical pains and organic dysfunctions causing significant morbidity and mortality. Therefore, the investigators need to establish guidelines in order to treat these pathologies. Standard treatments such as surgery or interventional radiology are of limited efficacy and related to a high level of recurrences as well as complications. Recent preclinical studies have shown the important role of the PI3Kinase/AKT/mTor pathway on the development and the venous/lymphatic vascular organisations suggesting an appealing therapeutic target to treat patients with venous, lympathic or complex vascular malformations.
Investigators will realize a multicentric phase III study enrolling a higher number of patients to statistically evaluate the efficacy and the safety of the Rapamycin, an mTOR inhibitor, in the treatment of children and adults with vascular malformations for which conventional therapies such as surgery or sclerotherapy are ineffective or associated with high risk of important complications. Nearly 250 patients (200 adults and 50 children) will be enrolled in several european centers.
- Conditions
- Vascular Malformations
- Being tested
- Sirolimus
- Medical subject headings
- Vascular Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycine
evaluate the efficacy and safety of sirolimus in these patients
| Study group | Role | What they receive |
|---|---|---|
| Patients with vascular malformations | Experimental | Patients with venous, lympathic or complex vascular malformations (KTS, PTEN, etc.) will receive sirolimus after completion of inclusion criteria Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
Measured by quality of life questionnaire (adapted to MOS SF-36 survey).
Measured: 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.
Relative change of volume of the vascular malformation between the baseline MRI (before sirolimus onset) and the 12-month MRI (during sirolimus treatment)
Measured: At 12 month
Efficacy of sirolimus
Change in plasma levels fibrinogen and/ or D-dimers, reflecting improvement in an abnormal intravascular coagulation consumption
Measured: every three months, up to 2-year period
Efficacy of sirolimus measured on digital photographs
Qualitative assessment of efficacy on digital photographs
Measured: every three months, up to 2-year period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2015 (estimated)
- Study start25 Jan 2016
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Apr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Vascular MalformationsStudies of the same condition, open and under way.
- More trials run by Cliniques universitaires Saint-Luc- Université Catholique de LouvainThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laurence M Boon, MD, PhD, Principal investigator, Cliniques universitaires Saint-Luc- Université Catholique de Louvain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02638389
- Sponsor's protocol ID
- VASE
- Status last verified
- Feb 2023
- First submitted
- 9 Dec 2015
- Last updated
- 24 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Seront E, Van Damme A, 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;21(1):62. doi: 10.1186/s13023-025-04151-y.
PubMed 41366677Jiang X, Hu L, Lai J, Ge S, Chen H, Yang X, Lin X. Venous Malformations: Unraveling Latest Mechanisms and Bridging Gaps in Targeted Therapy Development. Int J Biol Sci. 2025 Oct 27;21(15):7013-7028. doi: 10.7150/ijbs.122569. eCollection 2025.
PubMed 41281754Seront 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.
PubMed 37937645
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Multicentric Study Evaluating the Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care
- ClinicalTrials.gov ID
- NCT02638389
- Acronym / sponsor ID
- VASE
- Conditions
- Vascular Malformations
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Cliniques universitaires Saint-Luc- Université Catholique de LouvainUniversity, hospital or other
- Study start
- 25 Jan 2016 (actual)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Apr 2030 (estimated)
- First posted
- 23 Dec 2015 (estimated)
- 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 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.
Detailed description
The complex vascular malformations induce chronical pains and organic dysfunctions causing significant morbidity and mortality. Therefore, the investigators need to establish guidelines in order to treat these pathologies. Standard treatments such as surgery or interventional radiology are of limited efficacy and related to a high level of recurrences as well as complications. Recent preclinical studies have shown the important role of the PI3Kinase/AKT/mTor pathway on the development and the venous/lymphatic vascular organisations suggesting an appealing therapeutic target to treat patients with venous, lympathic or complex vascular malformations.
Investigators will realize a multicentric phase III study enrolling a higher number of patients to statistically evaluate the efficacy and the safety of the Rapamycin, an mTOR inhibitor, in the treatment of children and adults with vascular malformations for which conventional therapies such as surgery or sclerotherapy are ineffective or associated with high risk of important complications. Nearly 250 patients (200 adults and 50 children) will be enrolled in several european centers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with vascular malformations | Experimental | Drug: SirolimusPatients with venous, lympathic or complex vascular malformations (KTS, PTEN, etc.) will receive sirolimus after completion of inclusion criteria |
Who may qualify
- Ages
- 3 months to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (8 listed)
- 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.)
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 |
|---|---|---|
| SirolimusAlso: Rapamycineevaluate the efficacy and safety of sirolimus in these patients | Drug | Patients with vascular malformations |
Primary outcome
Self-assesment (or parent assesment), using visual anagogic scale (0-10) of efficacy of sirolimus
Time frame: every 3 months, up to 2-year period.
* Global treatment efficacy * Pain * Local complications/symptoms (bleeding, skin tension, esthetic and functional impairment)
5 secondary outcomes
Number of enrolled patients with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 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
Time frame: 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.
Time frame: At 12 month
Efficacy of sirolimus
Time frame: every three months, up to 2-year period
Efficacy of sirolimus measured on digital photographs
Time frame: every three months, up to 2-year period
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 24 Feb 2023.
- Derived from this study: PubMed 41366677Seront E, Van Damme A, 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;21(1):62. doi: 10.1186/s13023-025-04151-y.
- Derived from this study: PubMed 41281754Jiang X, Hu L, Lai J, Ge S, Chen H, Yang X, Lin X. Venous Malformations: Unraveling Latest Mechanisms and Bridging Gaps in Targeted Therapy Development. Int J Biol Sci. 2025 Oct 27;21(15):7013-7028. doi: 10.7150/ijbs.122569. eCollection 2025.
- Derived from this study: PubMed 37937645Seront 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.
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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.
Laurence M Boon, MD, PhD principal investigator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus in people with Vascular Malformations, run by Cliniques universitaires Saint-Luc- Université Catholique de Louvain at 3 sites in 3 countries.
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 9 inclusion and 8 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 24 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium, France, Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Laurence M. Boon, MD, PhD (+ 32-2-764 8020, laurence.boon@uclouvain.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Self-assesment (or parent assesment), using visual anagogic scale (0-10) of efficacy of sirolimus (time frame: every 3 months, up to 2-year period.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02638389, which also lists 3 linked publications.
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 24 Feb 2023.