Low-dose Intra-arterial Bevacizumab for Edema and Radiation Necrosis Therapeutic Intervention (LIBERTI)
Condition: Radiation Necrosis
MeSH terms: Necrosis
Intervention: 25% Mannitol; Low-dose Intra-arterial Bevacizumab
Intervention description: Route of administration:
In this study, the first step of the treatment will be performing osmotic blood-brain-barrier disruption with administration of intra-arterial 25% Mannitol into the appropriate cervical artery.; Route of administration:
In this study, the second step of the treatment will be administering intra-arterial targeted bevacizumab into the appropriate cervical artery.
Intervention MeSH terms: Bevacizumab; Mannitol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Radiation necrosis; Radiation adverse event; Intra-arterial chemotherapy; Bevacizumab; Blood brain barrier disruption; Blood brain barrier breakdown; Arteriovenous malformation; Stereotactic radiosurgery

Summary:

      To assess the overall safety and efficacy of intra-arterial (IA) bevacizumab for the
      treatment of radiation necrosis. A single 2.5 mg/kg dose of bevacizumab will be given
      intra-arterially after osmotic blood-brain-barrier disruption.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients must have radiation necrosis based on radiographic evidence defined as:

          -  Increased T1 contrast enhancement in the radiated area with central hypointensity

          -  Increased surrounding vasogenic edema on FLAIR MRI images

          -  The underlying lesion prompting the radiation can include: Benign lesions such as AVM,
             Meningioma, schwannoma, trigeminal neuralgia: No biopsy is necessary

          -  Radiation necrosis must be symptomatic, including either severe headache, seizures, or
             neurological deficits.

          -  Radiation necrosis must be refractory to steroid treatment; defined as failing a
             3-week steroid regiment or not tolerating steroids because of side effects. Beyond 3
             weeks, the side effects of steroid therapy worsen rapidly. The patient may receive
             other therapies such as Vitamine E, Pentoxyfylline, and hyperbaric oxygen during the
             trial.

        Other inclusion criteria include:

          -  Age >18 years.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Both men and women and members of all races and ethnic groups are eligible for this
             trial.

          -  Karnofsky Performance Status > or = 70%.

          -  Life expectancy of greater than 3 months.

          -  Patients must have normal organ and marrow function as defined below:

        leukocytes greater than equal to1,500/mcL platelets greater than equal to 85,000/mcL
        creatinine less than equal to 1.8 mg/dl

        •Birth Control: The effects of Bevacizumab on the developing human fetus are unknown. For
        this reason, women of childbearing potential and men must agree to use adequate
        contraception (hormonal or barrier method of birth control; abstinence) prior to study
        entry and for the duration of study participation. Should a woman become pregnant or
        suspect she is pregnant while participating in this study, she should inform her treating
        physician immediately. Women of childbearing age will have a urine pregnancy test
        immediately before each IA Bevacizumab treatment.

        Exclusion Criteria:

          -  Patients may not be started on any other investigational agents during the course of
             this trial. They may however continue previous medical regiments aimed for treatment
             of radiation necrosis. These include steroids, vitamin E, pentoxiphylline, and
             hyperbaric oxygen. We feel that these treatments are generally ineffectual and would
             not confound the results.

          -  Malignant brain tumor

          -  Concomitant use of anticoagulation agents including Coumadin, anticoagulation dose
             Lovenox or Arixtra. Aspirin is acceptable.

          -  Active bleeding or pathological condition that carries high risk of bleeding.

          -  Abdominal fistula, abscess, or gastrointestinal tract perforation 28 days of study
             entry.

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Any major surgery in the prior 4 weeks. Also any major surgery expected to be
             performed in the ensuing 4 weeks after treatment.

          -  Pregnant women are excluded from this study because Bevacizumab is expected to disrupt
             angiogenesis during pregnancy with the potential for teratogenic or abortive effects.
             Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with Bevacizumab, breastfeeding should be
             discontinued if the mother is treated with Bevacizumab.

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with Bevacizumab.