Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma

January 23, 2024 updated by: John Boockvar, MD Zucker SOM @Hofstra/Northwell, Northwell Health

Phase I/II Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory Glioblastoma Multiforme And Anaplastic Astrocytoma

The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in median overall survival durations of only 9-12 months for GBM, and 3-4 years for AA. Initial therapy consists of either surgical resection, external beam radiation or both. All patients 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). The investigators have shown in a previous phase I trial that a single Superselective Intraarterial Cerebral Infusion (SIACI) of Bevacizumab (up to 15mg/kg) is safe and effective in the treatment of recurrent GBM. Therefore, this phase I/II clinical research trial is an extension of that trial in that the investigators seek to test the hypothesis that repeated dosing of intra-arterial Bevacizumab is safe and effective in the treatment of recurrent malignant glioma. Additionally the investigators will analyze if a combination with IA Carboplatin will further improve the treatment response. By achieving the aims of this study the investigators will also determine if IV therapy with Bevacizumab with IV Carboplatin should be combined with repeated selected intra-arterial Bevacizumab plus Carboplatin to improve progression free and overall survival. The investigators expect that this project will provide important information regarding the utility of repeated SIACI Bevacizumab therapy for malignant glioma, and may alter the way these drugs are delivered to the investigators patients in the near future.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10075
        • Lenox Hill Brain Tumor Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 years of age or older.
  • Documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA).
  • Circumscribed tumor recurrence with less than 3.5 cm greatest diameter
  • Patients with histologically confirmed low-grade brain tumor relapse with an enhancing tumor on MRI will be evaluated for toxicity only.
  • Patients must have at least one confirmed and evaluable tumor site.
  • Patients must have a Karnofsky performance status 70% (or the equivalent ECOG level of 0-2)
  • Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period.

Exclusion Criteria:

  • Women who are pregnant or lactating.
  • Patients with significant intercurrent 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.
  • Low GFR or history of hepatorenal syndrome

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 2
Drug: Bevacizumab and Carboplatin
Drug: Bevacizumab and Carboplatin

Day 0: Intraarterial Bevacizumab single dose (15mg/kg) plus Intraarterial Carboplatin (150mg/m2) after Mannitol to open the blood brain barrier

Day 28: Intravenous Bevacizumab (10mg/kg) plus Carboplatin (AUG5) every two weeks thereafter until disease progression on MRI scan.

If progression occurs, repeat intraarterial Bevacizumab single dose (15mg/kg) plus intraarterial Carboplatin (150mg/m2) to area of progression and wait 28 days and then restart Intravenous Bevacizumab (10mg/kg) plus Carboplatin (AUG5) every two weeks thereafter until progression on MRI scan.

Repeat Cycle

Drug: Bevacizumab and Carboplatin

Day 0: Intraarterial Bevacizumab single dose (15mg/kg) plus Intraarterial Carboplatin (150mg/m2) after Mannitol to open the blood brain barrier

Day 28: No biweekly IV Bevacizumab plus Carboplatin treatment

If MRI shows progression then repeat intraarterial Bevacizumab single dose (15mg/kg) plus intraarterial Carboplatin (150mg/m2) to area of progression Repeat Cycle
Experimental: Arm 1
Drug: Bevacizumab and Carboplatin
Drug: Bevacizumab and Carboplatin

Day 0: Intraarterial Bevacizumab single dose (15mg/kg) plus Intraarterial Carboplatin (150mg/m2) after Mannitol to open the blood brain barrier

Day 28: Intravenous Bevacizumab (10mg/kg) plus Carboplatin (AUG5) every two weeks thereafter until disease progression on MRI scan.

If progression occurs, repeat intraarterial Bevacizumab single dose (15mg/kg) plus intraarterial Carboplatin (150mg/m2) to area of progression and wait 28 days and then restart Intravenous Bevacizumab (10mg/kg) plus Carboplatin (AUG5) every two weeks thereafter until progression on MRI scan.

Repeat Cycle

Drug: Bevacizumab and Carboplatin

Day 0: Intraarterial Bevacizumab single dose (15mg/kg) plus Intraarterial Carboplatin (150mg/m2) after Mannitol to open the blood brain barrier

Day 28: No biweekly IV Bevacizumab plus Carboplatin treatment

If MRI shows progression then repeat intraarterial Bevacizumab single dose (15mg/kg) plus intraarterial Carboplatin (150mg/m2) to area of progression Repeat Cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite overall response rate
Time Frame: 6 months
The composite overall response rate (CORR) will be examined. The overall response proportion along with a 95% confidence interval will be estimated via binomial proportions.
6 months
Six-month progression-free survival (PFS) and overall survival (OS)
Time Frame: 2 years
PFS will be measured from the date of the first dose of SIACI Bevacizumab plus Carboplatin to the date of progression. OS will be measured from the date of the first dose of SIACI Bevacizumab plus Carboplatin to the date of death.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The safety of repeated SIACI of Mannitol, Bevacizumab plus Carboplatin at 15mg/kg and 150mg/m2 respectively.
Time Frame: 1 month
The descriptive frequency of subjects experiencing toxicities will also be tabulated. Toxicities will be assessed and graded according to the NCI Common Toxicity Criteria, version 3.0.
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwell Health

Investigators

  • Principal Investigator: John Boockvar, MD, Lenox Hill Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

June 13, 2011

First Submitted That Met QC Criteria

June 29, 2011

First Posted (Estimated)

July 1, 2011

Study Record Updates

Last Update Posted (Estimated)

January 24, 2024

Last Update Submitted That Met QC Criteria

January 23, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1012011410

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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