Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22

Phase 1

Terminated

• Conditions: Glioblastoma Multiforme; Fibrillary Astrocytoma of Brain; Glioma of Brainstem; Anaplastic Astrocytoma; Pilomyxoid Astrocytoma; Mixed Oligodendroglioma-Astrocytoma; Brain Stem Glioma; Diffuse Intrinsic Pontine Glioma
• Interventions: Drug: SIACI of Erbitux and Bevacizumab

• Registration Number: NCT01884740
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

Central nervous system (CNS) malignancies are the second most common malignancy and the most common solid tumor of childhood, including adolescence. Annually in the United States, approximately 2,200 children are diagnosed with CNS malignancy and rates appear to be increasing. CNS tumors are the leading cause of death from solid tumors in children. Survival duration after diagnosis in children is highly variable depending in part on age at diagnosis, location of tumor, and extent of resection; however, most children with high grade glioma die within 3 years of diagnosis. All patients with high grade glioma experience a recurrence after first-line therapy, so improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. It is unknown if currently used intravenous (IV) therapies even cross the blood brain barrier (BBB). We have shown in previous phase I trials that a single Superselective Intra-arterial Cerebral Infusion (SIACI) of Cetuximab and/or Bevacizumab is safe for the treatment of recurrent glioblastoma multiforme (GBM) in adults, and we are currently evaluating the efficacy of this treatment. Therefore, this phase I/II clinical research trial is an extension of that trial in that we seek to test the hypothesis that intra-arterial Cetuximab and Bevacizumab is safe and effective in the treatment of relapsed/refractory glioma in patients \<22 years of age. We expect that this project will provide important information regarding the utility of SIACI Cetuximab and Bevacizumab therapy for malignant glioma in patients \<22 years of age and may alter the way these drugs are delivered to our patients in the near future.

Detailed Description

The experimental aspects of this treatment plan will include:

1. Subjects will first be treated with Mannitol prior to chemotherapy infusion (Mannitol 25%; 10 mL over 2 minutes) in order to disrupt the blood brain barrier. This technique has been used in several thousand patients in previous studies for the IA delivery of chemotherapy for malignant glioma. We have used this without complication in our patients from our Phase I protocols as well.

2. To treat patients \<22 years of age with recurring or relapsing glioma with a single intraarterial delivery (SIACI) of Cetuximab and Bevacizumab. Our Phase I trials have demonstrated the safety of SIACI delivery of these drugs in adults. This trial will focus on the safety and efficacy in patients \<22 years of age.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2013-06-19
• Study First Submitted QC: 2013-06-19
• Study First Posted: 2013-06-24
• Primary Completion: 2018-10
• Study Completion: 2018-10
• Results First Submitted: 2022-06-08
• Status Verified: 2022-07
• Results First Submitted QC: 2022-07-14
• Last Update Submitted: 2022-07-14
• Results First Posted: 2022-08-09
• Last Update Posted: 2022-08-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 13

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SIACI of Erbitux and Bevacizumab	SIACI of Erbitux and Bevacizumab	Superselective Intraarterial Cerebral Infusion (SIACI) of Erbitux (200 mg/m\^2) and Bevacizumab (15 mg/kg)

Primary Outcome Measures

Name	Time	Method
Median Overall Survival (OS)	2 Years	Overall Survival (OS) will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of death.
Composite Overall Response Rate (CORR)	6 Months	The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions. The investigator will define "evaluable" patients as patients who met eligibility requirements and have initiated therapy.

Secondary Outcome Measures

Name	Time	Method
Number of Treatment Emergent Adverse Events	28 days	All treatment emergent adverse events will be assessed and graded according to Common Terminology Criteria for Adverse Events (CTCAE)v. 4.0 terminology for severity, duration, and relationship to research protocol treatment.
Median Progression-free Survival (PFS)	2 Years	PFS will be assessed by Kaplan-Meier survival analysis, assuming adequate follow-up time. PFS will be measured from the date of the first dose of SIACI Cetuximab/Avastin to the date of progression.

Trial Locations

Locations (1)

Weill Cornell Medical College/New York Presbyterian Hospital; 🇺🇸 New York, New York, United States