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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 ³.

Principal Investigator

Dr. Howard Fine, NCI Center for Cancer Research.

Dr. Howard A. Fine Principal Investigator

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 (VEGF receptor)," 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 ⁴.

Study Site 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.

Glossary Terms

A tumor located in the part of the brain that connects to the spinal cord (the brain stem). It may grow rapidly or slowly, depending on the grade of the tumor.

The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also called epidermal growth factor receptor, ErbB1, and HER1.

A term used to describe cells that look abnormal under a microscope. These cells are more likely to grow and spread quickly than cells in low-grade cancer or in growths that may become cancer.

A term used to describe cells that look nearly normal under a microscope. These cells are less likely to grow and spread more quickly than cells in high-grade cancer or in growths that may become cancer.

The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

Cancer that is growing, spreading, or getting worse.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrence.

A substance made by cells that stimulates new blood vessel formation. Also called vascular endothelial growth factor.

A substance that is being studied as a treatment for cancer. It belongs to the family of drugs called vascular endothelial growth factor-2 (VEGF-2) receptor antagonists.