Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab (Bevacizumab) For Treatment Of Relapsed/Refractory Glioblastoma Multiforme And Anaplastic Astrocytoma.
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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. |
- 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 ]
- 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 |
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| Contact: John Boockvar, MD | 212-746-1996 | jab2029@med.cornell.edu |
| Contact: Trisha Ali-Shaw | 212-746-7373 | tra2002@med.cornell.edu |
| 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 | |
| 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 June 17, 2013