Super-Selective Intraarterial Intracranial Infusion of Avastin (Bevacizumab) - Full Text View

Sponsor:	Weill Medical College of Cornell University
Information provided by:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT00968240

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). Superselective Intraarterial Cerebral Infusion (SIACI) is a technique that can effectively increase the concentration of drug delivered to the brain while sparing the body of systemic side effects. One currently used drug called, Bevacizumab (Avastin) has been shown to be active in human brain tumors but its actual CNS penetration is unknown. This phase I clinical research trial will test the hypothesis that Bevacizumab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 10mg/kg to ultimately enhance survival of patients with relapsed/refractory GBM/AA. By achieving the aims of this study we will determine the toxicity profile and maximum tolerated dose (MTD of SIACI Bevacizumab. We expect that this project will provide important information regarding the utility of SIACI Bevacizumab therapy for malignant glioma, and may alter the way these drugs are delivered to our patients in the near future.

Condition	Intervention	Phase
Glioblastoma Multiforme Anaplastic Astrocytoma	Drug: Super-Selective Intraarterial Intracranial Infusion of BEVACIZUMAB	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Trial of Super-Selective Intraarterial Intracranial Infusion of Avastin (Bevacizumab) For Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Bevacizumab

U.S. FDA Resources

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

Primary Outcome Measures:

To determine the safety of superselective intracranial intraarterial infusion of Avastin up to a dose of 10mg/kg IA. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary 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: 3 years ] [ Designated as safety issue: No ]
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: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	July 2009
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Intervention Details:

This phase I clinical research trial will test the hypothesis that Bevacizumab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 10mg/kg to ultimately enhance survival of patients with relapsed/refractory GBM/AA.

Day 0: Intraarterial Avastin single dose (starting at 2mg/kg and up to 10mg/kg) after Mannitol to open the blood brain barrier.

Other Name: Avastin

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Eligibility

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

Criteria

Inclusion Criteria:

Histologically confirmed diagnosis of recurrent GBM
Available tumor tissue for correlative analyses (frozen or paraffin-fixed, archived or recent)
Age > 18 years
Patients must have a Karnofsky performance status >=60% (or the equivalent ECOG level of 0-2) (see Appendix A; Performance Status Evaluation) and an expected survival of >= three months.
No chemotherapy for six weeks prior to treatment under this research protocol and no external beam radiation for eight weeks prior to treatment under this research protocol.
Patients must have adequate hematologic reserve with WBC >=3000/mm3, absolute neutrophils >=1500/mm3 and platelets >=100,000/ mm3. Patients who are on Coumadin must have a platelet count of >=150,000/ mm3
Pre-enrollment chemistry parameters must show: bilirubin<1.5X the institutional upper limit of normal (IUNL); AST or ALT<2.5X IUNL and creatinine<1.5X IUNL.
Pre-enrollment coagulation parameters (PT and PTT) must be =<1.5X the IUNL.
Concomitant Medications: Growth factor(s): Must not have received within 1 week of entry onto this study. Steroids: Systemic corticosteroid therapy is permissible in patients with CNS tumors for treatment of increased intracranial pressure or symptomatic tumor edema. Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.
Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study.
Patients must be able to understand and give written informed consent. Informed consent must be obtained at the time of patient screening.

Exclusion Criteria:

Patients previously treated with more than 6 cycles of Avastin at 10/mg/kg.
Women who are pregnant or lactating.
Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00968240

Contacts

Contact: John Boockvar, MD	212-746-1996	jab2029@nyp.org
Contact: Euphael Henry, MD	212-746-2438	euh2002@med.cornell.edu

Locations

United States, New York
Weill Cornell Medical College-New York Presbyterian Hospital	Recruiting
New York, New York, United States, 10065
Contact: John Boockvar, MD 212-746-1996 jab2029@med.cornell.edu
Contact: Euphael Henry, MD 212-746-2438 euh2002@med.cornell.edu
Principal Investigator: John Boockvar, MD
Principal Investigator: Howard Riina, MD
Sub-Investigator: Susan Pannullo, MD
Sub-Investigator: Philip E Stieg, MD
Sub-Investigator: Theodore Schwartz, MD
Sub-Investigator: Ronald Scheff, MD

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

Principal Investigator:	John Boockvar, MD	Weill Cornell Medical College-New York Presbyterian Hospital
Principal Investigator:	Howard Riina, MD	Weill Cornell Medical College- New York Presbyterian Hospital

More Information

No publications provided

Responsible Party:	John Boockvar MD, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT00968240 History of Changes
Other Study ID Numbers:	0901010185
Study First Received:	August 26, 2009
Last Updated:	January 5, 2011
Health Authority:	United States: Institutional Review Board

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 February 09, 2012