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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

About this trial

This is an interventional treatment trial for Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

NCT ID

NCT02800486

First Posted

May 27, 2016

Last Updated

October 17, 2022

Sponsor

Northwell Health

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

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

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

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

jboockvar@northwell.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Tamika Wong, MPH

Phone

212-434-4836

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

jboockvar@northwell.edu

First Name & Middle Initial & Last Name & Degree

Tamika Wong, MPH

Phone

212-434-4836

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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