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

Primary Purpose

Glioblastoma Multiforme, Anaplastic Astrocytoma, Fibrillary Astrocytomas

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SIACI of cetuximab and bevacizumab
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme

Eligibility Criteria

1 Year - 21 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Jackson Memorial Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SIACI of cetuximab and bevacizumab

Arm Description

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

Outcomes

Primary Outcome Measures

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.
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.
Progression-free survival (PFS)
PFS will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of progression.
Overall Survival (OS)
OS will be measured from the date of diagnosis to the date of death

Secondary Outcome Measures

Full Information

First Posted
July 14, 2023
Last Updated
September 25, 2023
Sponsor
University of Miami
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1. Study Identification

Unique Protocol Identification Number
NCT05956821
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
October 1, 2029 (Anticipated)
Study Completion Date
December 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme, Anaplastic Astrocytoma, Fibrillary Astrocytomas, Oligodendroglioma, Diffuse Intrinsic Brainstem Glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SIACI of cetuximab and bevacizumab
Arm Type
Experimental
Arm Description
Participants in this group will receive Cetuximab and Bevacizumab infusion into an artery each month for up to approximately one year.
Intervention Type
Drug
Intervention Name(s)
SIACI of cetuximab and bevacizumab
Other Intervention Name(s)
erbitux, avastin
Intervention Description
Subjects will receive monthly dosing of bevacizumab (15 mg/kg) and cetuximab (200mg/m2)
Primary Outcome Measure Information:
Title
Number of Treatment Related Adverse Events
Description
The number of treatment-related adverse events will be assessed and graded according to the NCI Common Toxicity Criteria, version 5.0.
Time Frame
1 month post injection
Title
Composite Overall Response Rate (CORR)
Description
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.
Time Frame
6 months
Title
Progression-free survival (PFS)
Description
PFS will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of progression.
Time Frame
1 year
Title
Overall Survival (OS)
Description
OS will be measured from the date of diagnosis to the date of death
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Heather McCrea, MD
Phone
305-585-3627
Email
hmccrea@med.miami.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heather McCrea, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jackson Memorial Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather McCrea, MD
Phone
305-585-3627
Email
hmccrea@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Heather McCrea, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34359048
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.
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Treatment of Relapsed/Refractory Intracranial Glioma in Patients Under 22 Years of Age

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