Efficacy and Safety of the Mammalian Target of Rapamycin (mTor Rapamycin) Inhibitor in Vascular Malformations (vasca-LM)

Clinical Study on Efficacy and Safety of the mTor Rapamycin Inhibitor Found in the Complex Vascular Malformations

The phosphatidylinositol 3-kinase (PI3Kinase)/Protein Kinase B (AKT)/mammalian target of rapamycin (mTor) pathway plays a role on the development and the lymphatic-vascular organisations.

The investigators want to study the efficacy and the safety of Rapamycin, an mTor inhibitor.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Abnormalities
• Intervention / Treatment: Drug: Sirolimus

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 lymphatic-vascular organisations suggesting an appealing therapeutic target to treat patients with complex vascular malformations.

The aim of this clinical study is to prospectively evaluate the efficacy and the safety of the Rapamycin, an mTOR inhibitor, to treat children and adults with microcystic lymphatic malformations, general lymphatics abnormalities (GLA) or complex vascular malformations for which conventional therapies as surgery or sclerotherapy are ineffective or associated with high risk of important complications.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-luc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with complex vascular abnormalities to be threat by a systemic therapy
• Patients must have adequate liver function (LDL-cholesterol, triglycerides,…)
• Patients must have adequate organ function: neutrophils >1500/mm³, Hb > 8,0 g et platelets> 50.000/mm³ (no platelets limits for the Kasabach Merritt syndrome)
• Patients must have adequate renal function(normal creatinin depending on the age), clearance > 70 ml/min/1.73m² and Urin Protein Creatinine ratio <0.3 g.
• Karnofsky or Landry > 50

Exclusion Criteria:

• Dental equipments or prosthesis interfering onto a radiological examen
• Other uncontrolled medical condition (uncontrolled diabetes, hypertension…)
• Concomitant drugs such as inhibitors/inducers of cytochrome P450 3A4 (CYP3A4)
• Immunocompromised patients, including known seropositivity for HIV
• Digestive problems modifying the absorption of Rapamycin (gastric tube feeding accepted)
• Pregnant or nursing (lactating) women
• Prior treatment with phosphatidylinositol 3-kinase (PI3K) and/or mTOR inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sirolimus; Seric level between 10 to 15 ng/ml Pills for the adults and liquid for the children. Twice a day.	Drug: Sirolimus; Other Names: rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time of duration of the treatment.(Efficacy)	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of adverse events observed	With Common Toxicity Criteria for Adverse Effects version 3	up to 12 months

Collaborators and Investigators

• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Investigators: Principal Investigator: Laurence Boon, MD, PhD, Cliniques Universitaires Saint-luc

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: October 5, 2012
• First Submitted That Met QC Criteria: March 12, 2013
• First Posted (Estimate): March 14, 2013

Study Record Updates

• Last Update Posted (Estimate): April 14, 2016
• Last Update Submitted That Met QC Criteria: April 13, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Vascular Abnormalities
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Vascular Malformations; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: vasca-LM