congenital vascular malformation : Vascular malformations can involve lymphatic vessels, capillaries, veins and arteries or even combinations. These vascular malformations are present at birth and grow with the child. MedDRA version: 20.0 Level: HLT Classification code 10047091 Term: Vascular malformations and acquired anomalies System Organ Class: 100000005125 MedDRA version: 20.0 Level: LLT Classification code 10047090 Term: Vascular malformation peripheral System Organ Class: 1000001586
Conditions
Interventions
Trade Name: Sirolimus or Rapamycin
Product Name: Sirolimus
Pharmaceutical Form: Coated tablet
INN or Proposed INN: SIROLIMUS
CAS Number: 53123-88-9
Sponsors
Radboud University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of Congenital venous malformation, or lymphatic malformation or combined. • Age between 1-60 years. • Patients (or legal guardians for children) have to be able to sign the informed consent • Patients are either refractory to standard care such as medical treatment (low molecular weight heparines, pain medication etc.), surgical resection and/or sclerotherapy/embolization (ineffective or accompanied by major complications) or there is no possibility for surgical intervention anymore. Only patients that have a normal clinical screening (no signs for infection, normal bone marrow function, normal liver and kidney function, normal glucose metabolism etc.) can be included. • Patients included have no cardiac impairment • Patients have no gastrointestinal impairment as Sirolimus is absorbed gastro-intestinal and normal function is needed • No other underlying medical disorder like Down syndrome or other syndromes • Women of reproductive age have to be informed that contraceptive methods are mandatory during the study time, pregnant women are excluded • Karnofsky score > 50 Are the trial subjects under 18? yes Number of subjects for this age range: 25 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 48 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: • No written informed consent • Known hypersensitivity to drugs or metabolites from similar classes as study treatment. • 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 • Impaired cardiac function or clinically significant cardiac diseases • Immunocompromised patients, including known seropositivity for HIV • Patient with any other concurrent severe and /or uncontrolled medical condition that would,in the investigator’s judgment, contraindicated participation in the clinical study. • Pregnant or lactating women • Karnofsky score < 50
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether Sirolimus results in a significant and clinically relevant reduction of pain and an improved quality of life in patients with untreatable vascular malformations.;Secondary Objective: What length of therapy is required to have and maintain adequate pain reduction? Will response to Sirolimus prolong after stop treatment or will there be a rebound? Will Sirolimus only have effect on pain reduction or will Sirolimus also inhibit growth/progression of the vascular malformation or even lead to reduction of the size of the vascular malformation? Which long term consequences can be observed after treatment with Sirolimus e.g. in children? Are there genetic factors in the vascular malformation that can predict outcome of treatment with Sirolimus? Will Sirolimus lead to a more cost-effective treatment for this patient group?;Primary end point(s): Endpoints will be evaluated after a time period of six months treatment with Sirolimus: Evaluation of Pain Quality of Life MRI of the vascular malformation ;Timepoint(s) of evaluation of this end point: Evaluation will be performed at time point zero: pain evaluation MRI of the vascular malformation Quality of life assesment And will subsequently re-evaluated after the treatment period of six months with sirolimus | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Will Sirolimus also inhibit growth/progression of the vascular malformation or even lead to reduction of the size of the vascular malformation? Based on the case reports described in literature, there is a good chance that Sirolimus leads to regression of the vascular malformation. Although this is not the primary objective of the present study, we would like to gain more insight in the percentage of patients this effect can be seen. For this, MRI of the vascular malformation will be made at the beginning of the study and after six months of treatment with Sirolimus. An experienced radiologist will evaluate the evolution of the volume of the malformation Are there genetic factors in the vascular malformation that can predict outcome of treatment with Sirolimus? Further insight in genotype-phenotype-correlation for venous and/or lymphatic malformations might offer the possibility for better, personalized treatment. It is the question whether Sirolimus will have a positive effect in those patients were no mutation could be found in one of the known genes (PIK3CA/ GNAQ/ AKT-1/ RASA / PTEN/ TIE-2/ Glomulin) involved in vascular malformations. Depending on the results of the present study, we will investigate whether this can be used for further individualization of treatment. Adverse events: short and long term consequences of treatment with Sirolimus All adverse events occurring will be entered in the Castor Database and scored using the CTCAE criteria version four. Subsequently, at the end of the study all data will be analyzed in SPSS using Chi-square analyses. Will the administration of Sirolimus lead to a more cost-effective treatment One of the secondary objectives is to evaluate whether the administration of Sirolimus indeed leads to a more cost effective treatment for patients with venous and/or lymphatic malformation. For this reason a cost-effectiveness analysis will be performed from a societal perspective and in ac | — |
Countries
Netherlands
Contacts
Public Contactwerkgroep@hecovan.nl
HECOVAN
Outcome results
None listed