Sirolimus efficacy in the treatment of vascular anomalies

Phase 1

Conditions: Complex vascular anomalies causing debilitating functional and esthetic impairment that are resistant to standard care
MedDRA version: 20.1Level: HLTClassification code 10047047Term: Vascular anomalies congenital NECSystem Organ Class: 100000004850
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2015-001703-32-BE

Lead Sponsor: Cliniques Universitaires Saint-Luc (CUSL)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 250

Inclusion Criteria

Inclusion is limited to children and adults from 3 months* to 70 years old:
* In Germany the inclusion is limited to adults only from 18 to 70 years old

-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)- – ref. page 57: Clinical parameters / diagnosis : Given the lack of response to conventional treatment ( compression stockings , anti- pain, low molecular weight heparin , sclerotherapy and / or surgery) (Dompmartin et al Phlebology 2010)
-Patients must have adequate bone marrow function: Hemoglobine> 10,0 g/dl, neutrophils >1500/mm³ and platelets > 100.000/mm³. Except for infants with hemangioendothelioma with risk of Kasabach-Merritt phenomenon (very low platelet count (lower than 80 000/mm3).
-Patients must have the following laboratory values:
oTotal 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)
oSerum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x ULN
oSerum 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.
-Absence of severe proteinuria
-Karnofsky > 50
-Parents or legal relatives have to be able to sign the informed consent

Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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.)
•Recent history of primary malignancy = 5 years, including history of non-melanoma skin cancer, but with with exception of carcinoma in situ of cervix.
•Immunocompromised patients, including known seropositivity for HIV
•Pregnant or lactating women
•Prior treatment with PI3K and/or mTOR inhibitors

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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