Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma
Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma
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 Superselective 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
 intra-arterial Bevacizumab is safe and effective in the treatment of recurrent malignant
 glioma. Additionally the investigators will analyze if a combination with IA Carboplatin will
 further improve the treatment response. By achieving the aims of this study the investigators
 will also determine if IV therapy with Bevacizumab with IV Carboplatin should be combined
 with repeated selected intra-arterial Bevacizumab plus Carboplatin 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 investigators patients in the near
 future.
Inclusion Criteria:

 -  18 years of age or older.

 -  Documented histologic diagnosis of relapsed or refractory glioblastoma multiforme
 (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA).

 -  Circumscribed tumor recurrence with less than 3.5 cm greatest diameter

 -  Patients with histologically confirmed low-grade brain tumor relapse with an enhancing
 tumor on MRI will be evaluated for toxicity only.

 -  Patients must have at least one confirmed and evaluable tumor site.

 -  Patients must have a Karnofsky performance status 70% (or the equivalent ECOG level of
 0-2)

 -  Patients must agree to use a medically effective method of contraception during and
 for a period of three months after the treatment period.

 Exclusion Criteria:

 -  Women who are pregnant or lactating.

 -  Patients with significant intercurrent medical or psychiatric conditions that would
 place them at increased risk or affect their ability to receive or comply with
 treatment or post-treatment clinical monitoring.

 -  Low GFR or history of hepatorenal syndrome