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

NCT02861898 | Recruiting Phase 1

• 1 other identifier: HS16-0257
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioblastoma; Brain Cancer; Brain Neoplasm; Brain Tumor; Brain Neoplasm, Malignant; EGFR Gene Overexpression; GBM

Keywords

EGFR; Epidermal Growth Factor Receptor; EGFRvIII

Outcome Measures

Primary Outcomes (2)

• 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

• Overall Survival (OS)

  OS will be calculated as the time from treatment initiation to the date of death.

  2 years

Secondary Outcomes (2)

• Composite overall response rate (CORR) through the Response Assessment in Neuro-Oncology (RANO)

  6 months

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

  6 months

Study Arms (1)

Intra-arterial Cetuximab after BBBD

EXPERIMENTAL

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

Interventions

Intra-arterial Cetuximab DRUG

Intra-arterial Cetuximab after BBBD

Intra-arterial Mannitol DRUG

Intra-arterial Cetuximab after BBBD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Lenox Hill Brain Tumor Center

New York, New York, 10075, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; 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

Central Study Contacts

John Boockvar, MD

CONTACT

212-434-4836; jboockvar@northwell.edu

Tamika Wong, MPH

CONTACT

212-434-4836; twong4@northwell.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 5, 2016
• First Posted: August 10, 2016
• Study Start: June 1, 2016
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)