Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study (METAFORE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT00843440
First received: February 12, 2009
Last updated: May 29, 2013
Last verified: October 2009
  Purpose

The efficacy of anti-VEGF treatments such as Bevacizumab in cases of HHT can be considered because of the molecular mechanisms implied in angiogenesis and HHT, as well as the mechanisms of action of this type of treatment. Two articles that have recently reported spectacular improvement thanks to Bevacizumab in patients with HHT complicated with severe liver involvement and cardiac effects support us in this sense.

Up to now, the only treatment recommended in the severe hepatic forms of HHT is a liver transplant, the disadvantages of which are both multiple and well known: long waiting lists, surgical morbidity and mortality, immunosuppressive treatment for life. Furthermore, treatment with Bevacizumab is not a contraindication, should the drug be ineffective, for a subsequent liver transplant if necessary.


Condition Intervention Phase
Hemorrhagic Hereditary Telangiectasia
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Bevacizumab for the Treatment Hemorrhagic Hereditary Telangiectasia (HHT) Associated With Severe Hepatic Vascular Malformations. Phase II Study.

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • cardiac output measured at 3 months [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluation at 6 and 12 months [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: March 2009
Study Completion Date: March 2012
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab
Study using a Gehan design, 7 patients will be included in the first phase and 18 additional patients will enter the second phase.
Drug: Bevacizumab
5 mg / kg every 14 days with a total of 6 injections.A two-phase Gehan method will be used with a first phase designed to eliminate a non effective treatment quickly and a second phase allowing assessment of efficacy.
Other Name: AVASTIN

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • General criteria:

    • Age ≥ 18 years and < 70 years
    • Subjects must have given their free and enlightened consent and have signed the consent form.
  • HHT related criteria

    • Patients monitored for clinically confirmed HHT disease.
    • Patients with severe liver involvement in relationship with the HHT disease
    • Patients with a high cardiac output on ultrasound.
  • Associated disease related criteria

    • Blood: neutrophil ≥ 1.0x109 / L and platelets ≥ 100x109 / L.
    • INR (International Normalized Ratio) ≤ 1.5 (except for patients on anticoagulants) and TCA ≤ 1.5 x upper limit of the standard laboratory
    • Renal function: creatinine ≤ 1.25 x upper limit of the standard laboratory. Patients who proteinuria to strip ≥ 2 + will have control of the Proteinuria of 24 hours to be ≤ 1g / 24 hours

Exclusion Criteria:

  • • General criteria
  • Women who are pregnant or liable to become pregnant in the course of the trial.
  • Patients who have reached their majority but who are protected by the terms of the law (French public health code).
  • Refusal to give enlightened consent.
  • Patients who are not affiliated to a health insurance regime

    • Criteria for the medical history

  • Patients in whom the diagnosis of HHT disease has not been confirmed.
  • The presence of atrial fibrillation on the electrocardiogram at the inclusion.
  • The presence of cerebral arteriovenous malformations on the angioMRI done in the year prior to inclusion.
  • Existence of diverticulitis of the colon or sigmoid
  • Thrombosis within 6 months before inclusion
  • Infectious disease treated by antibiotics and unresolved at inclusion.
  • Patients with blood pressure that is not being controlled at the time of inclusion (systolic blood pressure> 150 mmHg and / or diastolic> 100 mmHg) with or without treatment. Patients who have high blood pressure can be included when the blood pressure numbers have been standardized by appropriate medical treatment.

    • Surgical criteria

  • Major surgery (including open biopsy) or severe trauma within 28 days preceding the start of treatment.

    • Medical treatments

  • Current or recent use of non steroidal anti-inflammatory drugs or antiplatelet therapy 10 days before the first administration of Bevacizumab.
  • Use of oral or parenteral anticoagulants or thrombolytic agents within 28 days preceding inclusion (anticoagulants given prophylactically are permitted).
  • Participation in another clinical trial within 28 days preceding inclusion.
  • Vaccination with live vaccines or against yellow fever during the treatment period.
  • Administration of phenytoin (Di-hydan ® DILANTIN ®) during the treatment period.

    • Allergy

  • Hypersensitivity to the active substance or any of its excipients.
  • Hypersensitivity to products made from Chinese hamster ovary (CHO) cells or to any other human or humanized recombinant antibodies.
  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: NCT00843440

Locations
France
Hospices Civils de Lyon
Lyon, France
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Sophie DUPUIS-GIROD, MD Hospices Civils de Lyon
  More Information

Additional Information:
No publications provided by Hospices Civils de Lyon

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT00843440     History of Changes
Other Study ID Numbers: 2008.510/11
Study First Received: February 12, 2009
Last Updated: May 29, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:
Antiangiogenic therapies
Bevacuzimab
Hemorrhagic Hereditary Telangiectasia (HHT) with severe liver involvement

Additional relevant MeSH terms:
Vascular Malformations
Congenital Abnormalities
Telangiectasis
Vascular Diseases
Cardiovascular Diseases
Cardiovascular Abnormalities
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014