Clinical Trial: Repeated Super-selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Relapsed GBM and AA

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase I/II Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab (Avastin) for Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic

Brief Summary: The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in median overall survival durations of only 9-12 months for GBM, and 3-4 years for AA. Initial therapy consists of either surgical resection, external beam radiation or both. All patients experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood brain barrier (BBB). The investigators have shown in a previous phase I trial that a single Super-selective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (up to 15mg/kg) is safe and effective in the treatment of recurrent GBM. Therefore, this phase I/II clinical research trial is an extension of that trial in that the investigators seek to test the hypothesis that repeated dosing of intraarterial Bevacizumab is safe and effective in the treatment of recurrent malignant glioma. By achieving the aims of this study the investigators will also determine if IV therapy with Bevacizumab should be combined with repeated selected intraarterial Bevacizumab to improve progression free and overall survival. The investigators expect that this project will provide important information regarding the utility of repeated SIACI Bevacizumab therapy for malignant glioma, and may alter the way these drugs are delivered to the patients in the near future.

Detailed Summary:

The current standard of care for recurring GBM is for patients to receive Bevacizumab (Avastin) intravenously (IV) at 10mg/kg every two weeks until their tumor grows more than 25%. At that point, these patients are deemed treatment failures and are given another treatment. Because of the blood brain barrier (BBB) where IV drugs do not penetrate the blood vessel walls well to get into the brain, no one knows for sure if these IV drugs actually get into the brain after infusion. We have recently completed a Phase I clinical trial that has shown that SIACI of Bevacizumab is safe and effective up to a dose of 15mg/kg in patients with recurrent malignant glioma. This two arm open-label, non-randomized trial is a follow up study to that trial and will ask two simple questions: Is it safe to deliver repeated doses of Bevacizumab intraarterially using these super selective intraarterial delivery techniques? Is it necessary to combine this IA regimen of treatment with biweekly IV Bevacizumab in order to improve progression free survival (PFS) and overall survival (OS)? Information from this trial will yield important answers to the durability and efficacy of this delivery technique and may radically change the way chemotherapy is given to our patients with brain tumors.

Current Standard of Care:

Day 0: Intravenous Bevacizumab (10mg/kg) Day 14, 28 (and every two weeks thereafter): Intravenous Bevacizumab

Therefore the experimental aspects of this treatment plan will include:

  1. Subjects will first be treated with Mannitol prior to chemotherapy infusion (Mannitol 20%; 12.5 mL/s over 2 minutes) in order to disrupt the blood brain barrier. This technique has been used in several thousand patients in previous
    Sponsor: Northwell Health

    Current Primary Outcome:

    • Composite overall response rate (CORR) [ Time Frame: 6 months ]
      We will determine this composite overall response rate (CORR) through the Response Assessment in Neuro-Oncology (RANO) criteria
    • Progression-free survival (PFS) and overall survival (OS) [ Time Frame: 6 month ]
      Six-month progression-free survival (PFS) and overall survival (OS) will be assessed by Kaplan-Meier survival analysis, assuming adequate follow-up time


    Original Primary Outcome:

    • Composite overall response rate: The composite overall response rate (CORR) will be examined. The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions. [ Time Frame: 6 months ]
    • Six-month progression-free survival PFS will be measured from the date of the first dose of SIACI Bevacizumab to the date of progression. OS will be measured from the date of the first dose of SIACI Bevacizumab to the date of death. [ Time Frame: 2 years ]


    Current Secondary Outcome: The safety of repeated SIACI of mannitol and Bevacizumab at 15mg/kg. [ Time Frame: 1 month ]

    The descriptive frequency of subjects experiencing toxicities will also be tabulated.


    Original Secondary Outcome: The safety of repeated SIACI of mannitol and Bevacizumab at 15mg/kg. The descriptive frequency of subjects experiencing toxicities will also be tabulated. [ Time Frame: 1 month ]

    Information By: Northwell Health

    Dates:
    Date Received: December 22, 2010
    Date Started: October 2010
    Date Completion: October 2017
    Last Updated: July 25, 2016
    Last Verified: July 2016