Name of the Trial
Phase I/II Study of ZD6474 in Patients with Recurrent High-Grade or Progressive Low-Grade Gliomas. See the protocol summary at http://www.cancer.gov/clinicaltrials/NCI-06-C-0063.

Principal Investigator
Dr. Howard Fine, NCI CCR

Why This Trial Is Important
Malignant glioma, the most common type of brain tumor, relies on the formation of new blood vessels to maintain its growth and to invade nearby tissue. Consequently, researchers are exploring the use of antiangiogenic agents - drugs that stop the growth of new blood vessels - to treat malignant gliomas.

A new drug called Zactima (ZD6474) targets both blood vessel growth and tumor cells themselves. "It binds to two key molecular targets, one on the tumor (EGFR) and one on blood vessels (VEGFR)," explained Dr. Fine. This disrupts cell-signaling pathways that the cancer cells need to grow and survive. Other drugs for malignant glioma may bind to one or the other of these targets, said Dr. Fine, but "we hope hitting them both together will increase [antitumor] activity."

Many patients with malignant glioma take a type of drug called an enzyme-inducing anti-epileptic drug (EIAED) to help control cancer-induced seizures. Patients taking EIAEDs need higher doses of Zactima because EIAEDs cause Zactima to be processed faster by the body. The phase I part of this trial will determine the dose of Zactima required for patients taking EIAEDs. The phase II part will enroll patients not taking EIAEDs, and will look at Zactima's antitumor activity.

Preliminary results of the trial have been promising, said Dr. Fine. "We've already seen signs of significant biologic activity and some tumor shrinkage. Though not in every patient, we're definitely seeing some very profound effects."

Who Can Join This Trial
Ninety-four patients with recurrent or progressive high-grade glioma who have had prior surgery and radiation therapy will be enrolled in the trial. Patients with low-grade glioma or infiltrative brain stem glioma may be eligible for the phase I part of the trial. See the list of eligibility criteria at http://cancer.gov/clinicaltrials/NCI-06-C-0063.

Study Sites and Contact Information
The study is taking place at the NIH Clinical Center in Bethesda, Md. For more information, call the NCI Clinical Studies Support Center at 1-888-NCI-1937. The toll-free call is completely confidential.