Phase I Trial of Super-Selective Intraarterial Intracranial Infusion of Avastin (Bevacizumab) For Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma

The current standard of care for recurring GBM is for patients to receive Bevacizumab (Avastin) intravenously (IV) at 10mg/kg with CPT-11 (Irinotecan) 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. Previous studies have shown that if you want to increase your penetration of drug to the brain, that intra-carotid artery (intraarterial) delivery is superior to standard intravenous delivery. Previous techniques using intra arterial (intracarotid) infusion still were non-selective as drug delivery still went to all blood vessels in the brain, so patients still had significant adverse events, such as blindness. Newer techniques in interventional neuroradiology have allowed for a more selective delivery of catheters higher up into the arterial tree where agents such as chemotherapies, can be delivered without the risk of adverse affects such as blindness. In fact, studies here at Cornell and MSKCC have developed very new and exciting super selective intraarterial delivery treatment for Pediatric Eye Tumors with little toxicity. Therefore, this trial will ask one simple question: Is it safe to delivery a patient's first dose of Avastin intraarterially using these super selective delivery techniques instead of the standard intravenous route of administration? This should not only increase the amount of drug that gets to the tumor but also spare the patient any adverse effects from a less selective delivery. During that single dose of intraarterial Avastin, the patient will also receive a dose of mannitol that opens up the blood brain barrier to improve delivery of the agent to the brain. After that single dose of Mannitol and Avastin intraarterially, the patient will be evaluated for 4 weeks to assess for toxicity. If no toxicity, then the patient will go on and get the standard chemotherapy (Avastin and CPT-11) every two weeks as is routine unless they fail. After this you are done with the "experimental" aspects of the protocol. This is a Phase I trial that is designed to test the safety of the single dose intraarterial delivery of Avastin and Mannitol, prior to starting standard IV Avastin and CPT-11.

In summary:

Current Standard of Care:

Day 0: Intravenous Avastin (10mg/kg) and CPT-11 Day 14, 28 (and every two weeks thereafter): Intravenous Avastin and CPT-11

Experimental portion of this proposal: