Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations (MAV-RAPA)

February 7, 2023 updated by: Centre Hospitalier Universitaire, Amiens

The aim of the study is to evaluate the efficacy and safety of sirolimus (oral form), to decrease the volume and symptoms due to superficial arteriovenous malformations (AVM).

Sirolimus has properties that reduce the activity of the immune system (immunosuppressant), to fight against the proliferation of cancer cells (anti- tumor) and also reduce the proliferation of blood vessels (anti -vascular). Sirolimus is primarily used in transplant patients to prevent organ transplant rejection. Many animal and laboratory studies were carried out and demonstrate in particular the activity of sirolimus on vessels. It is this anti- vascular effect that could help treat arteriovenous malformations.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Anti-proliferative and anti-angiogenic properties of Sirolimus (Rapamycin®) are the basis of the rationale to use it in the treatment of arteriovenous malformations, for which the pathophysiology remains poorly understood. The interest of this class of drug is that inhibition of mTOR (mammalian target of rapamycin) may also block growth and / or angiogenic factors (other than VEGF) involved in the development of AVM. More specifically anti-VEGF drugs does not have that potential.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Bruxelles, Belgium
        • Not yet recruiting
        • UCL
  • France
      • Amiens, France, 80000
        • Recruiting
        • CHU Amiens
      • Bordeaux, France, 33000
        • Not yet recruiting
        • CHU Bordeaux
      • Dijon, France, 21000
        • Recruiting
        • CHU Dijon
      • Lille, France, 59000
        • Not yet recruiting
        • CHRU Lille
      • Lyon, France, 69000
        • Recruiting
        • HCL LYON
      • Marseille, France, 13000
        • Not yet recruiting
        • APHM
      • Montpellier, France, 34000
        • Not yet recruiting
        • CHU Montpellier
      • Nancy, France, 54000
        • Not yet recruiting
        • CHU Nancy
      • Nice, France, 06000
        • Not yet recruiting
        • CHU Nice
      • Paris, France, 75000
        • Not yet recruiting
        • APHP
      • Strasbourg, France, 67000
        • Not yet recruiting
        • CHU Strasbourg
      • Tours, France, 37000
        • Not yet recruiting
        • CHU Tours

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients (adults, adolescents and children older than 2 years), with arteriovenous malformation stage II + III or IV (according to Schöbinger's classification) : active or quiescent, marked or not by hemorrhagic phenomena.
  • Patients (parents for minors) must sign a consent form established after clear information risks and expected benefits of the study.
  • Patients (major and minor of childbearing age) must have effective contraception during the study period and continuing until 12 weeks after the end of treatment
  • Negative pregnancy blood test for women of childbearing age.

Exclusion Criteria:

  • Chronic or acquired immunosuppression :

    • patients with transplanted organ or who received a hematopoietic stem cell
    • patient with congenital immunodeficiency
  • Patients implanted with chronic active infection associated with hepatitis B , hepatitis C or HIV
  • Pregnant or nursing woman.
  • Allergy to macrolides
  • Allergy to peanut or soya
  • Hypersensitivity to " Sirolimus " or any of the excipients of the investigational product
  • Contraindications to performing an MRI
  • Leukopenia below 1 000 /mm3
  • Thrombocytopenia lower to 80,000 /mm3
  • Anemia with Hb < 9 g/dl
  • Elevated transaminase > 2.5 N
  • History of cancer less than two years before the inclusion
  • Surgery older than 2 months before inclusion
  • Active infection (viral and bacterial ) on the date of inclusion
  • Hypercholesterolemia > 7 mmol / l despite appropriate medical treatment
  • Hyperlipidemia > 2 mmol / l despite appropriate medical treatment
  • Uncontrolled diabetes
  • Patients unable to follow a clinical study
  • Major under guardianship, persons deprived of their liberty

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Sirolimus treatment

Patients will receive sirolimus (Rapamune). The dose should be adjusted to obtain a residual plasma rate of 8 to 12 ng/ml in 4 weeks. This serum level will be maintained throughout the duration of the study in the absence of side effects. In case of intolerance that do not justify the discontinuation of treatment, the dose may be reduced by maintaining a serum level greater than 3 ng/ml.

The starting dose will be 2 mg per day, and will be adapted every week for one month.

The preferred dosage form is tablet form. To prevent common side effects in early treatment, corticosteroids based prednisolone (SOLUPRED) will be established at a dose of 0.5 mg/ kg/day for the first week of treatment.
Drug: Sirolimus
For patients with swallowing problems, and for children under 6 years and / or who have an inability to swallow tablets, the 1mg/ml solution form should be used.
Other Names:
  • Rapamune

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment efficacy at M12
Time Frame: After 12 months of treatment

The efficacy of treatment is a composite criteria based on:

  • The proportion of patients with no evolution of the AVM during the study period,
  • The proportion of patients with a reduction in tumor volume of the AVM at least 30% of CT Angiography (CTA) criteria during the first year of the study (comparison of the volume of the AVM a year versus pre-inclusion).
After 12 months of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment efficacy at M3
Time Frame: After 3 months of treatment
After 3 months of treatment
Treatment efficacy at M6
Time Frame: After 6 months of treatment
After 6 months of treatment
Treatment efficacy at M9
Time Frame: After 9 months of treatment
After 9 months of treatment
Treatment tolerability
Time Frame: One year
Number and description of serious advent events
One year
Treatment Impact on Quality of life
Time Frame: Before treatment initiation and after 12 months of treatment
Quality of life will be assessed before and at the end of the first year of treatment using a questionnaire given to patients. There is no questionnaire specifically tailored to vascular malformations in the literature. Thus the investigators adapted a document based on an evaluation of the quality of life for survivors of burn injury.
Before treatment initiation and after 12 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire, Amiens

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 12, 2014

Primary Completion (ANTICIPATED)

September 1, 2024

Study Completion (ANTICIPATED)

September 1, 2024

Study Registration Dates

First Submitted

January 20, 2014

First Submitted That Met QC Criteria

January 20, 2014

First Posted (ESTIMATE)

January 22, 2014

Study Record Updates

Last Update Posted (ACTUAL)

February 8, 2023

Last Update Submitted That Met QC Criteria

February 7, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PHRCN10-PR-DEVAUCHELLE
  • 2011-000321-69 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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