Phase I Trial of Super-Selective Intraarterial Cerebral Infusion of Cetuximab (Erbitux) for Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma

There is no current standard of care for recurring GBM after patients receive Bevacizumab (Avastin) intravenously (IV) at 10mg/kg with CPT-11 (Irinotecan). At that point, these patients are deemed treatment failures and are given another experimental 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 intraarterial (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 have developed very new and exciting super selective intraarterial delivery treatments for Retinoblastoma, eye tumors with little toxicity and a clinical trial of intraarterial delivery of Avastin is currently underway for GBM. Therefore, this trial will ask one simple question: Is it safe to deliver a dose of Cetuximab 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. Prior to that single dose of intraarterial Cetuximab, 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 Cetuximab intraarterially, the patient will be evaluated for 4 weeks to assess for toxicity. After this point, the patient is done with the "experimental" aspects of the protocol. If no toxicity at this point, then the patient will go on and get their chosen chemotherapy as determined by their treating oncologist. In summary, this is a Phase I trial that is designed to test the safety of a single dose of intraarterial delivery of Mannitol and Cetuximab , prior to starting the patients next round of chosen chemotherapy

To summarize:

Current Standard of Care Therapy : None

Experimental portion of this proposal:

Day 0: Intraarterial Mannitol to open the blood brain barrier followed by Intraarterial Cetuximab single dose (starting at 100mg/m2 and up to 500mg/m2)