Clinical Trials /

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

NCT02800486

Description:

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.

Related Conditions:
  • Anaplastic Astrocytoma
  • Anaplastic Oligoastrocytoma
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Super Selective Intra-arterial Repeated Infusion of <span class="go-doc-concept go-doc-intervention">Cetuximab (Erbitux)</span> With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA

Title

  • Brief Title: Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA
  • 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
  • Clinical Trial IDs

    NCT ID: NCT02800486

    ORG ID: HS16-0181

    Trial Conditions

    Glioblastoma

    Anaplastic Astrocytoma

    Anaplastic Oligoastrocytoma

    Glioma

    Brain Neoplasm

    Brain Cancer

    Brain Tumor

    Brain Tumor, Recurrent

    Brain Neoplasm, Malignant

    Trial Interventions

    Drug Synonyms Arms
    Intra-arterial Cetuximab Intra-arterial Cetuximab with Re-Irradiation
    Intra-arterial Mannitol Intra-arterial Cetuximab with Re-Irradiation

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Intra-arterial Cetuximab with Re-Irradiation Experimental 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 Intra-arterial Cetuximab, Intra-arterial Mannitol

    Eligibility 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 WBC3000/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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival (PFS)

    Overall Survival (OS)

    Secondary Outcome Measures

    Composite overall response rate (CORR) through the Response Evaluation Criteria In Solid Tumors (RECIST)

    Toxicities graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03

    Trial Keywords