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

NCT02042326 | Unknown Phase 2 DMC

• 2 other identifiers: PHRCN10-PR-DEVAUCHELLE2011-000321-69
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 13

Brief Summary

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.

Conditions

Arteriovenous Malformations

Keywords

Arteriovenous Malformations; Sirolimus; Maxillofacial Surgery

Outcome Measures

Primary Outcomes (1)

• Treatment efficacy at M12

  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 Outcomes (5)

• Treatment efficacy at M3

  After 3 months of treatment

• Treatment efficacy at M6

  After 6 months of treatment

• Treatment efficacy at M9

  After 9 months of treatment

• Treatment tolerability

  One year

• Treatment Impact on Quality of life

  Before treatment initiation and after 12 months of treatment

Study Arms (1)

Sirolimus treatment

EXPERIMENTAL

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

Interventions

Sirolimus DRUG

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.

Also known as: Rapamune

Sirolimus treatment

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Hypercholesterolemia \> 7 mmol / l despite appropriate medical treatment
• Hyperlipidemia \> 2 mmol / l despite appropriate medical treatment

Sponsors & Collaborators

• Centre Hospitalier Universitaire, Amiens: lead

Study Sites (13)

UCL

Brussels, Belgium

NOT YET RECRUITING

CHU Amiens

Amiens, 80000, France

RECRUITING

CHU Bordeaux

Bordeaux, 33000, France

NOT YET RECRUITING

CHU Dijon

Dijon, 21000, France

RECRUITING

CHRU Lille

Lille, 59000, France

NOT YET RECRUITING

HCL Lyon

Lyon, 69000, France

RECRUITING

APHM

Marseille, 13000, France

NOT YET RECRUITING

CHU Montpellier

Montpellier, 34000, France

NOT YET RECRUITING

CHU Nancy

Nancy, 54000, France

NOT YET RECRUITING

CHU Nice

Nice, 06000, France

NOT YET RECRUITING

APHP

Paris, 75000, France

NOT YET RECRUITING

CHU Strasbourg

Strasbourg, 67000, France

NOT YET RECRUITING

CHU Tours

Tours, 37000, France

NOT YET RECRUITING

MeSH Terms

Conditions

Arteriovenous Malformations

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Vascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Bernard DEVAUCHELLE, MD, PhD

  CHU Amiens

  STUDY DIRECTOR

• Emmanuel MORELON, MD, PhD

  HCL Lyon

  STUDY CHAIR

Central Study Contacts

Bernard DEVAUCHELLE, MD, PhD

CONTACT

+33322668325; devauchelle.bernard@chu-amiens.fr

Sylvie TESTELIN, MD, PhD

CONTACT

testelin.sylvie@chu-amiens.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2014
• First Posted: January 22, 2014
• Study Start: September 12, 2014
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); FR (12)