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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor:
Information provided by (Responsible Party):
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier:
NCT01811667
First received: October 5, 2012
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Cardiovascular Abnormalities
Drug: Sirolimus
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Study on Efficacy and Safety of the mTor Rapamycin Inhibitor Found in the Complex Vascular Malformations

Resource links provided by NLM:


Further study details as provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:

Primary Outcome Measures:
  • Time of duration of the treatment.(Efficacy) [ Time Frame: Radiologic and clinic evaluations on month 3, 6 and up to 12 months. ] [ Designated as safety issue: No ]
    Radiological, physical exams and quality of life.


Secondary Outcome Measures:
  • The number of adverse events observed [ Time Frame: After one week, one month and up to 12 months ] [ Designated as safety issue: Yes ]
    With Common Toxicity Criteria for Adverse Effects version 3


Estimated Enrollment: 60
Study Start Date: May 2012
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Rapamycine

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.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01811667

Locations
Belgium
Cliniques universitaires Saint-Luc Recruiting
Brussels, Belgium, 1200
Contact: Laurence Boon, MD, PhD    32-2-764 ext 80 20    laurence.boon@uclouvain.be   
Contact: Aline Gillain, Med Science    32-2-764 ext 54 70    aline.gillain@uclouvain.be   
Principal Investigator: Laurence Boon, MD, PhD         
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Investigators
Principal Investigator: Laurence Boon, MD, PhD Cliniques universitaires Saint-Luc
  More Information

No publications provided

Responsible Party: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT01811667     History of Changes
Other Study ID Numbers: vasca-LM
Study First Received: October 5, 2012
Last Updated: March 12, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
Vascular Abnormalities

Additional relevant MeSH terms:
Vascular Malformations
Congenital Abnormalities
Cardiovascular Abnormalities
Cardiovascular Diseases
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 24, 2014