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

Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNorthwell Health

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

18 years of age or older.

Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA).

Patients must have at least one confirmed and evaluable tumor site. A confirmed tumor site is one in which is biopsy-proven.

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

Disqualifiers

Previous treatment with greater than 2 cycles of Bevacizumab at 10mg/kg (2 IV Infusions).

Women who are pregnant or lactating.

Patients with significant inter-current 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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Bevacizumab

    Drug

    Experimental portion of this proposal: This trial will have two experimental arms that will be open labeled and non-randomized. ARM 1 (If the patient has multifocal disease or leptomeningeal disease) Day 0: Intraarterial Bevacizumab single dose (15mg/kg) after Mannitol to open the blood brain barrier Day 28: Intravenous Bevacizumab (10mg/kg) every two weeks thereafter until disease progression on MRI scan. If progression occurs, repeat Intraarterial Bevacizumab single dose (15mg/kg) to area of progression and wait 28 days and then restart Intravenous Bevacizumab (10mg/kg) every two weeks thereafter until progression on MRI scan. Repeat Cycle

  • Bevacizumab

    Drug

    ARM 2 (If the patient has no multifocal disease or leptomeningeal disease) Day 0: Intraarterial Bevacizumab single dose (15mg/kg) after Mannitol to open the blood brain barrier Day 28: No biweekly IV Bevacizumab treatment If MRI shows progression then repeat Intraarterial Bevacizumab single dose (15mg/kg) to area of progression Repeat Cycle

Treatment groups

54 Participants
are divided into 2 treatment groups
Group A: Arm 2Experimental treatment 1 intervention
Group B: Arm 1Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Composite overall response rate (CORR)

We will determine this composite overall response rate (CORR) through the Response Assessment in Neuro-Oncology (RANO) criteria

Time frame
6 months
2

Progression-free survival (PFS) and overall survival (OS)

Six-month progression-free survival (PFS) and overall survival (OS) will be assessed by Kaplan-Meier survival analysis, assuming adequate follow-up time

Time frame
6 month

Secondary outcomes

1

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Northwell Health

Lead sponsor

Feinstein Institute for Medical Research

Sponsor institution

Feinstein Institute for Medical Research

Collaborator