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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by Centre Hospitalier Universitaire, Amiens
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire, Amiens
ClinicalTrials.gov Identifier:
NCT02042326
First received: January 20, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Arteriovenous Malformations (Stage II to IV)
Drug: Sirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Evaluation of the Efficacy of Sirolimus (Rapamune®) in the Treatment of Severe Arteriovenous Malformations

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire, Amiens:

Primary Outcome Measures:
  • Treatment efficacy at M12 [ Time Frame: After 12 months of treatment ] [ Designated as safety issue: No ]

    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).


Secondary Outcome Measures:
  • Treatment efficacy at M3 [ Time Frame: After 3 months of treatment ] [ Designated as safety issue: No ]
  • Treatment efficacy at M6 [ Time Frame: After 6 months of treatment ] [ Designated as safety issue: No ]
  • Treatment efficacy at M9 [ Time Frame: After 9 months of treatment ] [ Designated as safety issue: No ]
  • Treatment tolerability [ Time Frame: One year ] [ Designated as safety issue: Yes ]
    Number and description of serious advent events

  • Quality of life [ Time Frame: Before treatment initiation and after 12 months of treatment ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 50
Study Start Date: January 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Rapamune

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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT02042326

Contacts
Contact: Bernard DEVAUCHELLE, MD, PhD +33322668325 devauchelle.bernard@chu-amiens.fr
Contact: Sylvie TESTELIN, MD, PhD testelin.sylvie@chu-amiens.fr

Locations
Belgium
UCL Not yet recruiting
Bruxelles, Belgium
France
CHU Amiens Not yet recruiting
Amiens, France, 80000
Principal Investigator: Bernard DEVAUCHELLE, MD, PhD         
Sub-Investigator: Sylvie TESTELIN, MD, PhD         
CHU Bordeaux Not yet recruiting
Bordeaux, France, 33000
CHU Dijon Not yet recruiting
Dijon, France, 21000
CHRU Lille Not yet recruiting
Lille, France, 59000
HCL Lyon Not yet recruiting
Lyon, France, 69000
APHM Not yet recruiting
Marseille, France, 13000
CHU Montpellier Not yet recruiting
Montpellier, France, 34000
CHU Nancy Not yet recruiting
Nancy, France, 54000
CHU Nice Not yet recruiting
Nice, France, 06000
APHP Not yet recruiting
Paris, France, 75000
CHU Strasbourg Not yet recruiting
Strasbourg, France, 67000
CHU Tours Not yet recruiting
Tours, France, 37000
Sponsors and Collaborators
Centre Hospitalier Universitaire, Amiens
Investigators
Study Director: Bernard DEVAUCHELLE, MD, PhD CHU Amiens
Study Chair: Emmanuel MORELON, MD, PhD HCL Lyon
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire, Amiens
ClinicalTrials.gov Identifier: NCT02042326     History of Changes
Other Study ID Numbers: PHRCN10-PR-DEVAUCHELLE, 2011-000321-69
Study First Received: January 20, 2014
Last Updated: January 20, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Centre Hospitalier Universitaire, Amiens:
Arteriovenous Malformations
Sirolimus
Maxillofacial Surgery

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

ClinicalTrials.gov processed this record on August 28, 2014