Super-Selective Intraarterial Cerebral Infusion of Cetuximab for the Treatment of Recurrent Glioblastoma Multiforme 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:
NCT01238237
First received: November 4, 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. 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, Cetuximab (Erbitux) 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 Cetuximab can be safely used by direct intracranial superselective intraarterial infusion up to a dose of 500mg/m2 to ultimately enhance survival of patients with relapsed/refractory GBM/AA. By achieving the aims of this study the investigators will determine the the toxicity profile and maximum tolerated dose (MTD) of SIACI Cetuximab. The investigators expect that this study will provide important information regarding the utility of SIACI Cetuximab 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 (GBM)
ANAPLASTIC ASTROCYTOMA (AOA)
Drug: Superselective Intraarterial Cerebral Infusion of Cetuximab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PHASE I TRIAL OF SUPER-SELECTIVE INTRAARTERIAL CEREBRAL INFUSION OF CETUXIMAB (ERBITUX) 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:
  • The maximum tolerated dose (MTD) of superselective intracerebral intraarterial Cetuximab. [ Time Frame: 1 month post procedure ] [ Designated as safety issue: Yes ]
  • descriptive frequency of subjects experiencing toxicities . [ Time Frame: throughout the study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Composite overall response rate [ Time Frame: 12 month ] [ Designated as safety issue: No ]
  • Six-month progression-free survival (PFS) and overall survival (OS). [ Time Frame: throughout the study. ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: December 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab Drug: Superselective Intraarterial Cerebral Infusion of Cetuximab
Intraarterial Mannitol 25% 3-10 ml to open the blood brain barrier followed by Intraarterial Cetuximab single dose (starting at 100mg/m2 and escalating up to 500mg/m2)
Other Name: Erbitux

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Male or female patients of greater than or equal to 18 years of age.
  • Patients with a documented histologic diagnosis of relapsed or refractory (malignant tumors that recur or resist treatment) glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA).
  • Patients must have at least one confirmed and evaluable tumor site. A confirmed tumor site is one in which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gd-enhanced MRI or CT scans) documenting existing lesions must have been performed within three weeks of treatment on this research study.
  • Patients must have a Karnofsky performance status greater than or equal to 60% (or the equivalent ECOG level of 0-2) (see Appendix A; Performance Status Evaluation) and an expected survival of greater than or equal to three months.
  • No chemotherapy for two weeks prior to treatment under this research protocol and no external beam radiation for two weeks prior to treatment under this research protocol.
  • Patients must have adequate hematologic reserve with WBC greater than or equal to 3000/mm3, absolute neutrophils greater than or equal to 1500/mm3 and platelets greater than or equal to 100,000/ mm3. Patients who are on Coumadin must have a platelet count of greater than or equal to 150,000/ mm3
  • Pre-enrollment chemistry parameters must show: bilirubin less than 1.5X the institutional upper limit of normal(IUNL); AST or ALT less than 2.5X IUNL and creatinine less than 1.5X IUNL.
  • Pre-enrollment coagulation parameters (PT and PTT) must be equal to or less than 1.5X the IUNL.
  • Concomitant Medications
  • 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. We do not believe that study procedures place subjects with increased intracranial pressure at any additional risk.
  • Study Specific Patients on enzyme-inducing anticonvulsants or non-enzyme inducing anticonvulsants will be allowed on the study. Patients receiving proton pump inhibitor or H2 blockers will be allowed on study. Patients taking antacids will be allowed on study.
  • 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 able to understand and give written informed consent and those patients that are cognitively impaired (which is common in GBM) are eligible for the trial. Informed consent must be obtained at the time of patient screening (prior to Day 0 of the procedure) either by the patient or a legalized authorized representative (LAR) of the patient ( health-care proxy).

Exclusion Criteria:

  • 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 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
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: NCT01238237

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- NewYork Presbyteryan Hospital Recruiting
New York, New York, United States, 10065
Contact: John Boockvar, MD    212-746-1996    jab2029@med.cornell.edu   
Contact: Trisha Ali-Shaw    212-746-7373    tra2002@med.cornell.edu   
Principal Investigator: John Boockvar, MD         
Sub-Investigator: Susan C. Pannullo, MD         
Sub-Investigator: Ronald Scheff, MD         
Sub-Investigator: Robert Zimmerman, MD         
Sub-Investigator: John A. Tsiouris, MD         
Sub-Investigator: Ehud Lavi, MD         
Sub-Investigator: Kane Prior, MD         
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
Principal Investigator: John Boockvar, MD Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: John A. Boockvar, Associate Professor, Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01238237     History of Changes
Other Study ID Numbers: 0909010652
Study First Received: November 4, 2010
Last Updated: December 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:
Glioblastoma Multiforme
Anaplastic Astrocytoma
High Grade Glial Neoplasms
Brain Tumor

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
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014