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Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma

This study is currently recruiting participants. (see Contacts and Locations)
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:
NCT01386710
First received: June 13, 2011
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. 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.


Condition Intervention Phase
Glioblastoma Multiforme
Anaplastic Astrocytoma
Drug: Bevacizumab and Carboplatin
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 Plus Carboplatin 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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.

  • Six-month progression-free survival (PFS) and overall survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    PFS will be measured from the date of the first dose of SIACI Bevacizumab plus Carboplatin to the date of progression. OS will be measured from the date of the first dose of SIACI Bevacizumab plus Carboplatin to the date of death.


Secondary Outcome Measures:
  • The safety of repeated SIACI of Mannitol, Bevacizumab plus Carboplatin at 15mg/kg and 150mg/m2 respectively. [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    The descriptive frequency of subjects experiencing toxicities will also be tabulated. Toxicities will be assessed and graded according to the NCI Common Toxicity Criteria, version 3.0.


Estimated Enrollment: 60
Study Start Date: September 2011
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 2
Drug: Bevacizumab and Carboplatin
Drug: Bevacizumab and Carboplatin

Day 0: Intraarterial Bevacizumab single dose (15mg/kg) plus Intraarterial Carboplatin (150mg/m2) after Mannitol to open the blood brain barrier

Day 28: No biweekly IV Bevacizumab plus Carboplatin treatment

If MRI shows progression then repeat intraarterial Bevacizumab single dose (15mg/kg) plus intraarterial Carboplatin (150mg/m2) to area of progression Repeat Cycle

Experimental: Arm 1
Drug: Bevacizumab and Carboplatin
Drug: Bevacizumab and Carboplatin

Day 0: Intraarterial Bevacizumab single dose (15mg/kg) plus Intraarterial Carboplatin (150mg/m2) after Mannitol to open the blood brain barrier

Day 28: Intravenous Bevacizumab (10mg/kg) plus Carboplatin (AUG5) every two weeks thereafter until disease progression on MRI scan.

If progression occurs, repeat intraarterial Bevacizumab single dose (15mg/kg) plus intraarterial Carboplatin (150mg/m2) to area of progression and wait 28 days and then restart Intravenous Bevacizumab (10mg/kg) plus Carboplatin (AUG5) every two weeks thereafter until progression on MRI scan.

Repeat Cycle


  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:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01386710

Contacts
Contact: John Boockvar, MD 212-746-1996 Jab2029@med.cornell.edu
Contact: Tamika Wong 212-746-1788 taw2015@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Sub-Investigator: Susan Pannullo, MD         
Sub-Investigator: Ehud Lavi, MD         
Sub-Investigator: John Tsiouris, MD         
Sub-Investigator: Zuzan Cayci, MD, PhD         
Sub-Investigator: Sherese Fralin, NP         
Sub-Investigator: Robert Zimmerman, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: John Boockvar, MD Weill Medical College of Cornell University
  More Information

Additional Information:
No publications provided

Responsible Party: John A. Boockvar, MD, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01386710     History of Changes
Other Study ID Numbers: 1012011410
Study First Received: June 13, 2011
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
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Bevacizumab
Carboplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014