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

Glioblastoma Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT02800486
• Other study ID #: HS16-0181
• Status: Recruiting
• Phase: Phase 2
• Start date: May 2016
• Est. completion date: May 2026

Study information

• Verified date: November 2023
• Source: Northwell Health
• Contact: John Boockvar, MD
• Phone: 212-434-3900
• Email: jboockvar[@]northwell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: May 2026
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anaplastic Astrocytoma
• Anaplastic Oligoastrocytoma
• Astrocytoma
• Brain Cancer
• Brain Neoplasm
• Brain Neoplasm, Malignant
• Brain Neoplasms
• Brain Tumor
• Brain Tumor, Recurrent
• Glioblastoma
• Glioma
• Neoplasms

Intervention

Drug:
• Intra-arterial Cetuximab

• Intra-arterial Mannitol

Radiation:
• Hypofractionated re-irradiation

Locations

Country	Name	City	State
United States	Lenox Hill Brain Tumor Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Northwell Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 months
Primary	Overall Survival (OS)	OS will be calculated as the time from treatment initiation to the date of death.	2 years
Secondary	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.	6 months
Secondary	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	6 months