Using Sirolimus to treat complex vascular anomalies that don't respond to standard care

Phase III Multicentric Study Evaluating the Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care

This study is testing if a medication called Sirolimus can help adults and children with complex vascular problems that haven't improved with standard treatments.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 250 (estimated)
• Ages: 3 Months to 70 Years
• Sex: All
• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain (Academic / other)
• Locations: 3 sites (Brussels, Brussels Capital and 2 other locations)
• Trial ID: NCT02638389 on ClinicalTrials.gov

What this trial studies

This phase III clinical trial aims to evaluate the efficacy and safety of Sirolimus, an mTOR inhibitor, in treating patients with complex vascular malformations that have not responded to conventional therapies such as surgery or sclerotherapy. The study will enroll approximately 250 patients, including both adults and children, across multiple European centers. By targeting the PI3Kinase/AKT/mTor pathway, the trial seeks to provide a new therapeutic option for patients suffering from significant morbidity and complications due to these vascular conditions.

Who should consider this trial

Good fit: Ideal candidates include patients with complex vascular anomalies that are refractory to standard care and have adequate medullary function.

Not a fit: Patients who have not been diagnosed with complex vascular anomalies or those who respond to standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with complex vascular anomalies, potentially reducing pain and improving quality of life.

How similar studies have performed: Previous studies have indicated the potential of targeting the mTOR pathway in vascular anomalies, suggesting that this approach may yield promising results.

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

Where this trial is running

Brussels, Brussels Capital and 2 other locations

• Cliniques Universitaires Saint-Luc, Université Catholique de Louvain Bruxelles — Brussels, Brussels Capital, Belgium (Recruiting)
• CHU Caen — Caen, Brittany Region, France (Recruiting)
• Universitätsklinikum Freiburg — Freiburg im Breisgau, Germany (Not_yet_recruiting)

Study contacts

• Principal investigator: Laurence M Boon, MD, PhD — Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Study coordinator: Laurence M. Boon, MD, PhD

Conditions Vascular Malformations