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Super-selective Intra-arterial Repeated Infusion of Cetuximab for the Treatment of Newly Diagnosed Glioblastoma

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ClinicalTrials.gov Identifier: NCT02861898
Recruitment Status : Recruiting
First Posted : August 10, 2016
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
John Boockvar, MD Zucker SOM @Hofstra/Northwell, Northwell Health

Brief Summary:

Primary brain cancer kills up to 10,000 Americans a year. These 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 EFGR (Epidermal Growth Factor Receptor) which is blocked by Cetuximab (CTX). The investigators have recently completed a separate Phase I clinical trial using superselective intra-arterial cerebral infusion (SIACI) of CTX after blood brain barrier disruption (BBBD) for recurrent GBM (Chakraborty et al, in revision, Journal of Neurooncology). The investigators found that intra-arterial infusion of CTX is well tolerated with few adverse effects. The investigators hypothesize that in patients with newly diagnosed GBM, repeated SIACI of this drug after BBBD will be safe and efficacious for our patients when combined with standard chemoradiation (STUPP protocol).

This trial will be a non-randomized open label Phase I/II clinical trial. In addition to standard chemotherapy and radiation therapy (STUPP protocol) the patient will be given CTX intra-arterially after BBBD for a total of three doses at approximately post surgery days 30, 120 and 210.


Condition or disease Intervention/treatment Phase
Glioblastoma Brain Cancer Brain Neoplasm Brain Tumor Brain Neoplasm, Malignant EGFR Gene Overexpression GBM Drug: Intra-arterial Cetuximab Drug: Intra-arterial Mannitol Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Super-selective Intra-arterial Repeated Infusion of Cetuximab for the Treatment of Newly Diagnosed Glioblastoma
Study Start Date : June 2016
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intra-arterial Cetuximab after BBBD
Mannitol 20% 12.5ml over two minutes for Blood Brain Barrier (BBB) disruption followed by CTX administered intra-arterially for three doses at a dose of 250mg/m2
Drug: Intra-arterial Cetuximab
Drug: Intra-arterial Mannitol



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 Assessment in Neuro-Oncology (RANO) [ Time Frame: 6 months ]
    Subjects will be classified according to the RANO 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 newly diagnosed glioblastoma multiforme (GBM)
  • 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. NOTE: Radiographic procedures (e.g., Gd-enhanced MRI or CT scans) documenting existing lesions must have been performed within two weeks of treatment on this research study.

  • Patients must have a Karnofsky performance status ≥70% (or the equivalent ECOG level of 0-2) 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 as to the potential 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 initiated or completed chemo/RT

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): NCT02861898


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

Locations
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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: Jed Pollack, MD         
Sub-Investigator: Anuj Goenka, MD         
Sub-Investigator: Christopher Filippi, MD         
Sub-Investigator: Sherese Fralin, NP         
Sub-Investigator: Ashley Ray, NP         
Sub-Investigator: Tamika Wong, MPH         
Sub-Investigator: Karissa Tan, NP         
Sub-Investigator: Shamik Chakraborty, MD         
Sponsors and Collaborators
Northwell Health

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Responsible Party: John Boockvar, MD Zucker SOM @Hofstra/Northwell, Principal Investigator, Northwell Health
ClinicalTrials.gov Identifier: NCT02861898     History of Changes
Other Study ID Numbers: HS16-0257
First Posted: August 10, 2016    Key Record Dates
Last Update Posted: May 17, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by John Boockvar, MD Zucker SOM @Hofstra/Northwell, Northwell Health:
EGFR
Epidermal Growth Factor Receptor
EGFRvIII
Additional relevant MeSH terms:
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Glioblastoma
Brain Neoplasms
Neoplasms
Astrocytoma
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, Immunological
Antineoplastic Agents
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs