Repeated Super-selective Intraarterial Cerebral Infusion of Bevacizumab (Avastin) for Treatment of Relapsed GBM and AA
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01269853|
Recruitment Status : Recruiting
First Posted : January 4, 2011
Last Update Posted : December 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme Anaplastic Astrocytoma||Drug: Bevacizumab||Phase 1 Phase 2|
The current standard of care for recurring GBM is for patients to receive Bevacizumab (Avastin) intravenously (IV) at 10mg/kg every two weeks until their tumor grows more than 25%. At that point, these patients are deemed treatment failures and are given another treatment. Because of the blood brain barrier (BBB) where IV drugs do not penetrate the blood vessel walls well to get into the brain, no one knows for sure if these IV drugs actually get into the brain after infusion. We have recently completed a Phase I clinical trial that has shown that SIACI of Bevacizumab is safe and effective up to a dose of 15mg/kg in patients with recurrent malignant glioma. This two arm open-label, non-randomized trial is a follow up study to that trial and will ask two simple questions: Is it safe to deliver repeated doses of Bevacizumab intraarterially using these super selective intraarterial delivery techniques? Is it necessary to combine this IA regimen of treatment with biweekly IV Bevacizumab in order to improve progression free survival (PFS) and overall survival (OS)? Information from this trial will yield important answers to the durability and efficacy of this delivery technique and may radically change the way chemotherapy is given to our patients with brain tumors.
Current Standard of Care:
Day 0: Intravenous Bevacizumab (10mg/kg) Day 14, 28 (and every two weeks thereafter): Intravenous Bevacizumab
Therefore the experimental aspects of this treatment plan will include:
- Subjects will first be treated with Mannitol prior to chemotherapy infusion (Mannitol 20%; 12.5 mL/s 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 the 30 patients from our Phase I protocol as well.
- To treat patients with one of two arms with repeated intraarterial delivery (SIACI) of Bevacizumab for patients with recurring or relapsing high grade glioma. Each arm gets IA delivery with one arm getting IV Bevacizumab biweekly as well and the other arm not getting intervening IV therapy. In each arm, IA therapy is repeated when MRI shows progression. Persistent progression after three intraarterial chemotherapies would remove the patient from the trial.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab (Avastin) for Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma.|
|Study Start Date :||October 2010|
|Estimated Primary Completion Date :||October 2018|
|Estimated Study Completion Date :||October 2018|
|Experimental: Arm 2||
Experimental portion of this proposal:
This trial will have two experimental arms that will be open labeled and non-randomized.
ARM 1 (If the patient has multifocal disease or leptomeningeal disease)
Day 0: Intraarterial Bevacizumab single dose (15mg/kg) after Mannitol to open the blood brain barrier Day 28: Intravenous Bevacizumab (10mg/kg) every two weeks thereafter until disease progression on MRI scan.
If progression occurs, repeat Intraarterial Bevacizumab single dose (15mg/kg) to area of progression and wait 28 days and then restart Intravenous Bevacizumab (10mg/kg) every two weeks thereafter until progression on MRI scan.
|Experimental: Arm 1||
ARM 2 (If the patient has no multifocal disease or leptomeningeal disease)
Day 0: Intraarterial Bevacizumab single dose (15mg/kg) after Mannitol to open the blood brain barrier Day 28: No biweekly IV Bevacizumab treatment
If MRI shows progression then repeat Intraarterial Bevacizumab single dose (15mg/kg) to area of progression Repeat Cycle
- Composite overall response rate (CORR) [ Time Frame: 6 months ]We will determine this composite overall response rate (CORR) through the Response Assessment in Neuro-Oncology (RANO) criteria
- Progression-free survival (PFS) and overall survival (OS) [ Time Frame: 6 month ]Six-month progression-free survival (PFS) and overall survival (OS) will be assessed by Kaplan-Meier survival analysis, assuming adequate follow-up time
- The safety of repeated SIACI of mannitol and Bevacizumab at 15mg/kg. [ Time Frame: 1 month ]The descriptive frequency of subjects experiencing toxicities will also be tabulated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01269853
|Contact: John Boockvar, MDfirstname.lastname@example.org|
|Contact: Tamika Wong, MPHemail@example.com|
|United States, New York|
|Lenox Hill Brain Tumor Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: John Boockvar, MD 212-434-3905 firstname.lastname@example.org|
|Principal Investigator: John Boockvar, MD|
|Sub-Investigator: David Langer, MD|
|Sub-Investigator: Rafael Ortiz, MD|
|Sub-Investigator: Alexis Demopolous, MD|
|Sub-Investigator: Ashley Ray, NP|
|Sub-Investigator: Tamika Wong, MPH|
|Sub-Investigator: Sherese Fralin, NP|
|Principal Investigator:||John Boockvar, MD||Feinstein Institute for Medical Research|