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NCT02638389 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
RECRUITING
Registry last update
2023-02-24

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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
healthy Volunteers
false
maximum Age
70 Years
minimum Age
3 Months
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients with venous, lympathic or complex vascular malformations (KTS, PTEN, etc.) will receive sirolimus after completion of inclusion criteria
    intervention Names
    1. Drug: Sirolimus
    label
    Patients with vascular malformations
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Patients with vascular malformations
    description
    evaluate the efficacy and safety of sirolimus in these patients
    name
    Sirolimus
    other Names
    1. Rapamycine
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
250
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    * Global treatment efficacy * Pain * Local complications/symptoms (bleeding, skin tension, esthetic and functional impairment)
    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.
secondary Outcomes
  1. measure
    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
  2. description
    Measured by quality of life questionnaire (adapted to MOS SF-36 survey).
    measure
    Self assessment of quality of life change induced by sirolimus
    time Frame
    every 3 months, up to 2-year period.
  3. description
    Relative change of volume of the vascular malformation between the baseline MRI (before sirolimus onset) and the 12-month MRI (during sirolimus treatment)
    measure
    Volumetric changes of the malformation on sirolimus, based on magnetic resonance imaging (MRI) 12 months after sirolimus onset.
    time Frame
    At 12 month
  4. description
    Change in plasma levels fibrinogen and/ or D-dimers, reflecting improvement in an abnormal intravascular coagulation consumption
    measure
    Efficacy of sirolimus
    time Frame
    every three months, up to 2-year period
  5. description
    Qualitative assessment of efficacy on digital photographs
    measure
    Efficacy of sirolimus measured on digital photographs
    time Frame
    every three months, up to 2-year period
Full study description
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.
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.
Source references
references
  1. citation
    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.
    pmid
    41366677
    type
    DERIVED
  2. citation
    Jiang 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.
    pmid
    41281754
    type
    DERIVED
  3. citation
    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
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        ame">TEK</em> variants appear to respond equally to treatment with sirolimus. Phase III clinical trials are underway in Europe (e.g., <a href="/clinicaltrials/NCT02638389">NCT02638389</a>, <a href="/clinicaltrials/NCT03987152">NCT03987152</a>, and <a href="/clinicaltrials/NCT04980872">NCT04980872</a>). A 2018 study reported pro
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        variants appear to respond equally to treatment with sirolimus. Phase III clinical trials are underway in Europe (e.g., <a href="/clinicaltrials/NCT02638389">NCT02638389</a>, <a href="/clinicaltrials/NCT03987152">NCT03987152</a>, and <a href="/clinicaltrials/NCT04980872">NCT04980872</a>). A 2018 study reported promising level
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      source title
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      source update dates
      1. context
        Updated: April 17, 2025
        datetime
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        display
        April 17, 2025

    Preserved source evidence · Not medical advice