Super-Selective Intraarterial Cerebral Infusion of Cetuximab (Erbitux) for Treatment of Relapsed/Refractory GBM and AA

NCT01238237 | Completed Phase 1

• 1 other identifier: 14-712
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma Multiforme (GBM); ANAPLASTIC ASTROCYTOMA (AOA); GBM; Anaplastic Astrocytoma

Keywords

Glioblastoma Multiforme; Anaplastic Astrocytoma; High Grade Glial Neoplasms; Brain Tumor; EGFR; Epidermal Growth Factor Receptor; EGFRvIII

Outcome Measures

Primary Outcomes (2)

• The maximum tolerated dose (MTD) of superselective intracerebral intraarterial Cetuximab.

  1 month post procedure

• descriptive frequency of subjects experiencing toxicities .

  throughout the study

Secondary Outcomes (2)

• Composite overall response rate

  12 month

• Six-month progression-free survival (PFS) and overall survival (OS).

  throughout the study.

Study Arms (1)

Cetuximab

EXPERIMENTAL

Drug: Superselective Intraarterial Cerebral Infusion of Cetuximab

Interventions

Superselective Intraarterial Cerebral Infusion of Cetuximab DRUG

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)

Also known as: Erbitux

Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Lenox Hill Brain Tumor Center

New York, New York, 10075, United States

Location

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Brain Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• John Boockvar, MD

  Feinstein Institute for Medical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neurosurgery

Study Record Dates

• First Submitted: November 4, 2010
• First Posted: November 10, 2010
• Study Start: December 1, 2009
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: February 1, 2017

Record last verified: 2017-01

Locations

US (1)