Low-dose Intra-arterial Bevacizumab for Edema and Radiation Necrosis Therapeutic Intervention (LIBERTI)

• Status: Completed
• Trial end date: 2019-06-06
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Norton Healthcare
• Collaborator: University of Kentucky
• Treatments: Bevacizumab; Mannitol

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.