Clinical trial NCT01386710: Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma
Official title: Phase I/II Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory Glioblastoma Multiforme And Anaplastic Astrocytoma
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme
Anaplastic Astrocytoma
Keywords: GBM
AA
AO
Brain
Tumors
Malignant
Glioblastoma
Multiforme
Anaplastic
Astrocytoma
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2011-07-01
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Composite overall response rate
timeFrame: 6 months
measure: Six-month progression-free survival (PFS) and overall survival (OS)
timeFrame: 2 years
Secondary outcomes:
measure: The safety of repeated SIACI of Mannitol, Bevacizumab plus Carboplatin at 15mg/kg and 150mg/m2 respectively.
timeFrame: 1 month
Other outcomes:
Locations:
city: New York
country: United States
facility: Lenox Hill Brain Tumor Center
state: New York
Study officials:
affiliation: Lenox Hill Hospital
name: John Boockvar, MD
role: PRINCIPAL_INVESTIGATOR
References: