Clinical trial NCT05956821: Treatment of Relapsed/Refractory Intracranial Glioma in Patients Under 22 Years of Age
Official title: Phase I/II Trial of Repeat Dosing of Super-Selective Intraarterial Infusion of Erbitux (Cetuximab) and Avastin (Bevacizumab) for Treatment of Relapsed/Refractory Intracranial Glioma in Patients Under 22 Years of Age
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Glioblastoma Multiforme
Anaplastic Astrocytoma
Fibrillary Astrocytomas
Oligodendroglioma
Diffuse Intrinsic Brainstem Glioma
Diffuse Intrinsic Pontine Glioma
DIPG Brain Tumor
H3 K27M
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2023-07-21
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Treatment Related Adverse Events
timeFrame: 1 month post injection
measure: Composite Overall Response Rate (CORR)
timeFrame: 6 months
measure: Progression-free survival (PFS)
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
Study officials:
affiliation: University of Miami
name: Heather McCrea, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.