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

• ClinicalTrials.gov Identifier: NCT01386710
• Recruitment Status: Suspended
• First Posted: July 1, 2011
• Last Update Posted: September 10, 2020
• Sponsor: Northwell Health
• Information provided by (Responsible Party): John Boockvar, MD Zucker SOM @Hofstra/Northwell, Feinstein Institute for Medical Research

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Glioblastoma Multiforme; Anaplastic Astrocytoma	Drug: Bevacizumab and Carboplatin	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2011
• Estimated Primary Completion Date: May 2022
• Estimated Study Completion Date: May 2022

Arms and Interventions

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: 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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, New York

Lenox Hill Brain Tumor Center

New York, New York, United States, 10075

Sponsors and Collaborators

Northwell Health

Investigators

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

More Information

Additional Information:

Drug Information available for: Bevacizumab 

Drug information for: Carboplatin 

• Responsible Party: John Boockvar, MD Zucker SOM @Hofstra/Northwell, MD, Feinstein Institute for Medical Research
• ClinicalTrials.gov Identifier: NCT01386710
• Other Study ID Numbers: 1012011410
• First Posted: July 1, 2011
• Last Update Posted: September 10, 2020
• Last Verified: September 2020

Keywords provided by John Boockvar, MD Zucker SOM @Hofstra/Northwell, Feinstein Institute for Medical Research:

GBM; AA; AO; Brain; Tumors; Malignant; Glioblastoma; Multiforme; Anaplastic; Astrocytoma

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Bevacizumab; Carboplatin; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors