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Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA

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ClinicalTrials.gov Identifier: NCT02800486
Recruitment Status : Recruiting
First Posted : June 15, 2016
Last Update Posted : March 1, 2018
Sponsor:
Information provided by (Responsible Party):
John A. Boockvar, Northwell Health

Brief Summary:
Primary brain tumors are typically treated by surgery, radiation therapy and chemotherapy, either individually or in combination. Present therapies are inadequate, as evidenced by the low 5-year survival rate for brain cancer patients, with median survival at approximately 12 months. Glioma is the most common form of primary brain cancer, afflicting approximately 7,000 patients in the United States each year. These highly malignant cancers remain a significant unmet clinical need in oncology. GBM often has a high expression of EFGR (Epidermal Growth Factor Receptor), which is associated with poor prognosis. Several methods of inhibiting this receptor have been tested, including monoclonal antibodies, vaccines, and tyrosine kinase inhibitors. The investigators hypothesize that in patients with recurring GBM, intracranial superselective intra-arterial infusion of Cetuximab (CTX), at a dose of 250mg/m2 in conjunction with hypofractionated radiation, will be safe and efficacious and prevent tumor progression in patients with recurrent, residual GBM.

Condition or disease Intervention/treatment Phase
Glioblastoma Anaplastic Astrocytoma Anaplastic Oligoastrocytoma Glioma Brain Neoplasm Brain Cancer Brain Tumor Brain Tumor, Recurrent Brain Neoplasm, Malignant Drug: Intra-arterial Cetuximab Drug: Intra-arterial Mannitol Radiation: Hypofractionated re-irradiation Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory Glioblastoma Multiforme, Anaplastic Astrocytoma, and Anaplastic Oligoastrocytoma
Actual Study Start Date : May 2016
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: Intra-arterial Cetuximab with Re-Irradiation
Mannitol 20% 12.5ml over two minutes for blood brain barrier (BBB) disruption followed by Cetuximab administered intra-arterially for three doses at a dose of 250 mg/m2 combined with hypofractionated re-irradiation
Drug: Intra-arterial Cetuximab
Drug: Intra-arterial Mannitol
Radiation: Hypofractionated re-irradiation



Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 6 months ]
    The 6-month PFS will be estimated by calculating the proportion of patients who are alive at 6 months from treatment commencement and are progression-free.

  2. Overall Survival (OS) [ Time Frame: 2 years ]
    OS will be calculated as the time from treatment initiation to the date of death.


Secondary Outcome Measures :
  1. Composite overall response rate (CORR) through the Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: 6 months ]
    Subjects will be classified according to the RECIST criteria, which is a composite of MRI changes, clinical response and changes in steroid use.

  2. Toxicities graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03 [ Time Frame: 6 months ]
    Toxicities will be tabulated and graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients of ≥18 years of age
  • Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic oligoastrocytoma (AOA)
  • Patients with pathology confirmed histologic EGFR overexpression
  • Patients must have at least one confirmed and evaluable tumor site.∗

    *A confirmed tumor site is one in which is biopsy-proven

  • Patients must have a Karnofsky performance status ≥60% and an expected survival of ≥ three months.
  • No chemotherapy for two 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
  • 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:

  • Women who are pregnant or lactating.
  • Women of childbearing potential and fertile men will be informed of the potential unknown risk of conception 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
  • Patients with radiological evidence of leptomeningeal disease
  • Patients with history of allergic reaction to CTX
  • Patients who completed chemo/RT less than 6 months prior to enrollment
  • Patients who have not failed standard Stupp protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02800486


Contacts
Contact: John Boockvar, MD 212-434-3900 jboockvar@northwell.edu
Contact: Tamika Wong, MPH 212-434-4836 twong4@northwell.edu

Locations
United States, New York
Lenox Hill Brain Tumor Center Recruiting
New York, New York, United States, 10075
Contact: John Boockvar, MD    212-434-3900    jboockvar@northwell.edu   
Contact: Tamika Wong, MPH    212-434-4836    twong4@northwell.edu   
Principal Investigator: John Boockvar, MD         
Sub-Investigator: David Langer, MD         
Sub-Investigator: Rafael Ortiz, MD         
Sub-Investigator: Alexis Demopoulos, MD         
Sub-Investigator: Jed Pollack, MD         
Sub-Investigator: Anuj Goenka, MD         
Sub-Investigator: Sherese Fralin, NP         
Sub-Investigator: Ashley Ray, NP         
Sub-Investigator: Karissa Tan, NP         
Sub-Investigator: Tamika Wong, MPH         
Sponsors and Collaborators
Northwell Health
Investigators
Principal Investigator: John Boockvar, MD Northwell Health

Responsible Party: John A. Boockvar, Principal Investigator, Northwell Health
ClinicalTrials.gov Identifier: NCT02800486     History of Changes
Other Study ID Numbers: HS16-0181
First Posted: June 15, 2016    Key Record Dates
Last Update Posted: March 1, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Neoplasms
Glioblastoma
Brain Neoplasms
Astrocytoma
Oligodendroglioma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
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
Cetuximab
Mannitol
Antineoplastic Agents
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs