Treatment of Relapsed/Refractory Intracranial Glioma in Patients Under 22 Years of Age

NCT05956821 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20230032
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study assesses the safety and efficacy of repeat monthly dosing of super-selective intra-arterial cerebral infusion (SIACI) of cetuximab and bevacizumab in patients \< 22 years of age.

Conditions

Glioblastoma Multiforme; Anaplastic Astrocytoma; H3 K27M; Fibrillary Astrocytomas; Oligodendroglioma; Diffuse Intrinsic Brainstem Glioma; Diffuse Intrinsic Pontine Glioma; DIPG Brain Tumor

Outcome Measures

Primary Outcomes (4)

• Number of Treatment Related Adverse Events

  The number of treatment-related adverse events will be assessed and graded according to the NCI Common Toxicity Criteria, version 5.0.

  1 month post injection

• Composite Overall Response Rate (CORR)

  The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions. We will define "evaluable" patients as patients who met eligibility requirements and have initiated therapy.

  6 months

• Progression-free survival (PFS)

  PFS will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of progression.

  1 year

• Overall Survival (OS)

  OS will be measured from the date of diagnosis to the date of death

  1 year

Study Arms (1)

SIACI of cetuximab and bevacizumab

EXPERIMENTAL

Participants in this group will receive Cetuximab and Bevacizumab infusion into an artery each month for up to approximately one year.

Drug: SIACI of cetuximab and bevacizumab

Interventions

SIACI of cetuximab and bevacizumab DRUG

Subjects will receive monthly dosing of bevacizumab (15 mg/kg) and cetuximab (200mg/m2)

Also known as: erbitux, avastin

SIACI of cetuximab and bevacizumab

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), fibrillary astrocytomas (FA), pilomyxoid astrocytoma (PXA), oligodendroglioma, or anaplastic mixed oligoastrocytoma (AOA), or radiologically diagnosed diffuse intrinsic brainstem glioma (DIPG)
• Must have at least one confirmed and evaluable tumor site
• Must have a Karnofsky or Lansky performance status ≥60%.
• No chemotherapy for three weeks prior to treatment
• Patients must have adequate hematologic reserve with absolute neutrophils≥1000/mm3 and platelets ≥100,000/ mm3
• Pre-enrollment chemistry parameters must show: bilirubin\<1.5x the institutional upper limit of normal (IUNL); Aspartate Aminotransferase( AST) or Alanine transaminase (ALT)\<2.5x IUNL and creatinine\<1.5x IUNL
• Pre-enrollment coagulation parameters (PT and PTT) must be ≤1.5x the IUNL
• Growth factor(s): Must not have received within 1 week of entry onto this study
• Steroids: Systemic corticosteroid therapy is permissible in patients with Central Nervous System (CNS) tumors for treatment of increased intracranial pressure or symptomatic tumor edema. Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.
• Patients of reproductive age 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 or their parents/guardians must be able to understand and give written informed consent. Informed consent must be obtained at the time of patient screening
• Because of known concerns with Avastin and wound healing, craniotomy patients are eligible for the treatment if they have had a craniotomy greater than two weeks prior to Intra-Arterial (IA) therapy. Craniotomy or major procedure after SIACI Avastin therapy should wait 4 weeks. Minor surgeries may be performed after two weeks

You may not qualify if:

• Females who are pregnant or lactating
• Females of childbearing potential and fertile men will be informed as to the potential risk of procreation 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. If they do not agree, they will be ineligible for the study
• Patients with significant concurrent 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

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

Jackson Memorial Hospital

Miami, Florida, 33136, United States

RECRUITING

Related Publications (1)

• McCrea HJ, Ivanidze J, O'Connor A, Hersh EH, Boockvar JA, Gobin YP, Knopman J, Greenfield JP. Intraarterial delivery of bevacizumab and cetuximab utilizing blood-brain barrier disruption in children with high-grade glioma and diffuse intrinsic pontine glioma: results of a phase I trial. J Neurosurg Pediatr. 2021 Aug 6;28(4):371-379. doi: 10.3171/2021.3.PEDS20738. Print 2021 Oct 1.

  PMID: 34359048 BACKGROUND

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Oligodendroglioma; Diffuse Intrinsic Pontine Glioma

Interventions

Bevacizumab; Cetuximab

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Heather McCrea, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heather McCrea, MD

CONTACT

305-585-3627; hmccrea@med.miami.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: Assistant Professor

Study Record Dates

• First Submitted: July 14, 2023
• First Posted: July 21, 2023
• Study Start: June 19, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)