Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA
Primary Purpose
Glioblastoma, Anaplastic Astrocytoma, Anaplastic Oligoastrocytoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Intra-arterial Cetuximab
Intra-arterial Mannitol
Hypofractionated re-irradiation
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma
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 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
Sites / Locations
- Lenox Hill Brain Tumor CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intra-arterial Cetuximab with Re-Irradiation
Arm Description
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
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS)
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.
Overall Survival (OS)
OS will be calculated as the time from treatment initiation to the date of death.
Secondary Outcome Measures
Composite overall response rate (CORR) through the Response Evaluation Criteria In Solid Tumors (RECIST)
Subjects will be classified according to the RECIST criteria, which is a composite of MRI changes, clinical response and changes in steroid use.
Toxicities graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03
Toxicities will be tabulated and graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02800486
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 2016 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwell Health
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma, Anaplastic Astrocytoma, Anaplastic Oligoastrocytoma, Glioma, Brain Neoplasm, Brain Cancer, Brain Tumor, Brain Tumor, Recurrent, Brain Neoplasm, Malignant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intra-arterial Cetuximab with Re-Irradiation
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Intra-arterial Cetuximab
Intervention Type
Drug
Intervention Name(s)
Intra-arterial Mannitol
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated re-irradiation
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
6 months
Title
Overall Survival (OS)
Description
OS will be calculated as the time from treatment initiation to the date of death.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Composite overall response rate (CORR) through the Response Evaluation Criteria In Solid Tumors (RECIST)
Description
Subjects will be classified according to the RECIST criteria, which is a composite of MRI changes, clinical response and changes in steroid use.
Time Frame
6 months
Title
Toxicities graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03
Description
Toxicities will be tabulated and graded according to the NCI Common Toxicity Criteria (CTCAE) version 4.03
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
John Boockvar, MD
Phone
212-434-3900
Email
jboockvar@northwell.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tamika Wong, MPH
Phone
212-434-4836
Email
twong4@northwell.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Boockvar, MD
Organizational Affiliation
Northwell Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lenox Hill Brain Tumor Center
City
New York
State/Province
New York
ZIP/Postal Code
10075
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Boockvar, MD
Phone
212-434-3900
Email
jboockvar@northwell.edu
First Name & Middle Initial & Last Name & Degree
Tamika Wong, MPH
Phone
212-434-4836
Email
twong4@northwell.edu
First Name & Middle Initial & Last Name & Degree
John Boockvar, MD
First Name & Middle Initial & Last Name & Degree
David Langer, MD
First Name & Middle Initial & Last Name & Degree
Rafael Ortiz, MD
First Name & Middle Initial & Last Name & Degree
Alexis Demopoulos, MD
First Name & Middle Initial & Last Name & Degree
Jed Pollack, MD
First Name & Middle Initial & Last Name & Degree
Anuj Goenka, MD
First Name & Middle Initial & Last Name & Degree
Sherese Fralin, NP
First Name & Middle Initial & Last Name & Degree
Ashley Ray, NP
First Name & Middle Initial & Last Name & Degree
Karissa Tan, NP
First Name & Middle Initial & Last Name & Degree
Tamika Wong, MPH
12. IPD Sharing Statement
Learn more about this trial
Super Selective Intra-arterial Repeated Infusion of Cetuximab (Erbitux) With Reirradiation for Treatment of Relapsed/Refractory GBM, AA, and AOA
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