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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Glioblastoma Multiforme, Anaplastic Astrocytoma, Fibrillary Astrocytomas, Oligodendroglioma, Diffuse Intrinsic Brainstem Glioma

Intervention / Treatment
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* Drug: SIACI of cetuximab and bevacizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SIACI of cetuximab and bevacizumab<br>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<br>* Subjects will receive monthly dosing of bevacizumab (15 mg/kg) and cetuximab (200mg/m2)<br>* Other names: avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |