Effects and treatment effect of sirolimus used against blood vessel deformities that are not suitable for surgical or other established treatment, or where established treatment has proven not to give satisfactory results

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-NO
• Lead Sponsor: Cliniques Universitaires Saint-Luc (CUSL)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-11-28
• Last Update Posted: 25 May 2020

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 1 year* to 70 years ( in Norway).
* In Belgium, the Netherlands and France 3 months to 70 years. In Germany 18 to 70 years.

-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

Patients must have the following laboratory values:
-Total serum bilirubin = 1.5 x ULN (Upper Limit Normal) 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 score > 50
-Patients have to be able to sign the informed consent
- For children, parents or legal relatives have to be able to sign the informed consent
-Women in age of reproduction have to be informed that contraceptive methods are mandatory during the study time

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 160
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 the 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