Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab (Bevacizumab) For Treatment Of Relapsed/Refractory Glioblastoma Multiforme And Anaplastic Astrocytoma.

This study is currently recruiting participants.
Verified December 2012 by Weill Medical College of Cornell University
Sponsor:
Information provided by (Responsible Party):
John A. Boockvar, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01269853
First received: December 22, 2010
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

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. By achieving the aims of this study the investigators will also determine if IV therapy with Bevacizumab should be combined with repeated selected intra-arterial 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.


Condition Intervention Phase
Glioblastoma Multiforme
Anaplastic Astrocytoma
Drug: Bevacizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab (Bevacizumab) For Treatment Of Relapsed/Refractory Glioblastoma Multiforme And Anaplastic Astrocytoma.

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: October 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 2 Drug: Bevacizumab
Day 0: Intraarterial Bevacizumab single dose (15mg/kg) after Mannitol to open the blood brain barrier Day 28 No IV Bevacizumab treatment If MRI shows progression then repeat Intraarterial Bevacizumab single dose (15mg/kg) to area of progression Repeat Cycle
Experimental: Arm 1 Drug: Bevacizumab

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


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

  • Previous treatment with greater than 6 months or 12 cycles of Bevacizumab at 10mg/kg.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01269853

Contacts
Contact: John Boockvar, MD 212-746-1996 jab2029@med.cornell.edu
Contact: Trisha Ali-Shaw 212-746-7373 tra2002@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College Department of Neurological Surgery 525 East 68th Street STARR 651 Recruiting
New York, New York, United States, 10065
Contact: John Boockvar, MD    212-746-1996    jab2029@med.cornell.edu   
Principal Investigator: John Boockvar, MD         
Sub-Investigator: Susan C. Pannullo, MD         
Sub-Investigator: Ehud Lavi, MD         
Sub-Investigator: John Tsiouris, MD         
Sub-Investigator: Philip Stieg, PhD, MD         
Sub-Investigator: Theodore Schwartz, MD         
Sub-Investigator: Ronald Scheff, MD         
Sub-Investigator: Robert Zimmerman, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: John Boockvar, MD Weill Cornell Medical College Department of Neurological Surgery
  More Information

No publications provided

Responsible Party: John A. Boockvar, Associate Professor, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01269853     History of Changes
Other Study ID Numbers: 1001010839
Study First Received: December 22, 2010
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
GBM
AA
AO
Brain
Tumors
Malignant
Glioblastoma
Multiforme
Anaplastic
Astrocytoma

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014