Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02638389
Recruitment Status : Recruiting
First Posted : December 23, 2015
Last Update Posted : June 14, 2017
Sponsor:
Information provided by (Responsible Party):
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Tracking Information
First Submitted Date  ICMJE December 9, 2015
First Posted Date  ICMJE December 23, 2015
Last Update Posted Date June 14, 2017
Study Start Date  ICMJE November 2015
Estimated Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2015)
Self-assesment (or parent assesment), using visual anagogic scale (0-10) of efficacy of sirolimus [ Time Frame: every 3 months, up to 2-year period. ]
  • Global treatment efficacy
  • Pain
  • Local complications/symptoms (bleeding, skin tension, esthetic and functional impairment)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2016)
  • Number of enrolled patients with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: every month during the first three months and then every three months for a 2-year-treatment period ]
  • Self assessment of quality of life change induced by sirolimus [ Time Frame: every 3 months, up to 2-year period. ]
    Measured by quality of life questionnaire (adapted to MOS SF-36 survey).
  • Volumetric changes of the malformation on sirolimus, based on magnetic resonance imaging (MRI) 12 months after sirolimus onset. [ Time Frame: At 12 month ]
    Relative change of volume of the vascular malformation between the baseline MRI (before sirolimus onset) and the 12-month MRI (during sirolimus treatment)
  • Efficacy of sirolimus [ Time Frame: every three months, up to 2-year period ]
    Change in plasma levels fibrinogen and/ or D-dimers, reflecting improvement in an abnormal intravascular coagulation consumption
  • Efficacy of sirolimus measured on digital photographs [ Time Frame: every three months, up to 2-year period ]
    Qualitative assessment of efficacy on digital photographs
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2015)
  • Number of enrolled patients with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: every month during the first three months and then every three months for a 2-year-treatment period ]
  • Self assessment of quality of life change induced by sirolimus [ Time Frame: every 3 months, up to 2-year period. ]
    Measured by quality of life questionnaire (adapted to MOS SF-36 survey).
  • Volumetric changes of the malformation on sirolimus, based on magnetic resonance imaging (MRI) 12 months after sirolimus onset. [ Time Frame: At 12 month ]
    Relative change of volume of the vascular malformation between the baseline MRI (before sirolimus onset) and the 12-month MRI (during sirolimus treatment)
  • Efficacy of sirolimus [ Time Frame: every three months, up to 2-year period ]
    Change in plasma levels fibrinogen and/ or D-dimers, reflecting improvement in an abnormal intravascular coagulation consumption
  • Efficacy of sirolimus measured on digital photographs [ Time Frame: every three months, up to 2-year period ]
    Qualitative assessment of efficacy on digital photographs
  • Organic collection of skin and blood samples [ Time Frame: at baseline, if feasible ]
    Translational research will be performed if feasible on blood and tissue sample, including genetic analysis of several genes involved in vasculogenesis (currently TIE2 and PIK3CA).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care
Official Title  ICMJE Phase III Multicentric Study Evaluating the Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care
Brief Summary

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

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

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 venous/lymphatic vascular organisations suggesting an appealing therapeutic target to treat patients with venous, lympathic or complex vascular malformations.

Investigators will realize a multicentric phase III study enrolling a higher number of patients to statistically evaluate the efficacy and the safety of the Rapamycin, an mTOR inhibitor, in the treatment of children and adults with vascular malformations for which conventional therapies such as surgery or sclerotherapy are ineffective or associated with high risk of important complications. Nearly 250 patients (200 adults and 50 children) will be enrolled in several european centers.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Vascular Malformations
Intervention  ICMJE Drug: Sirolimus
evaluate the efficacy and safety of sirolimus in these patients
Other Name: Rapamycine
Study Arms  ICMJE Experimental: Patients with vascular malformations
Patients with venous, lympathic or complex vascular malformations (KTS, PTEN, etc.) will receive sirolimus after completion of inclusion criteria
Intervention: Drug: Sirolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 18, 2015)
250
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2025
Estimated Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Months to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Laurence M. Boon, MD, PhD + 32-2-764 8020 laurence.boon@uclouvain.be
Listed Location Countries  ICMJE Belgium,   France,   Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02638389
Other Study ID Numbers  ICMJE VASE
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study Sponsor  ICMJE Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Laurence M Boon, MD, PhD Cliniques universitaires Saint-Luc
PRS Account Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP