Name of the Trial
Phase II Study of Vandetanib in Patients with Metastatic or Unresectable Clear Cell Renal Cell Carcinoma (NCI-08-C-0039). See the protocol summary at http://www.cancer.gov/clinicaltrials/NCI-08-C-0039.

Dr. W. Marston Linehan

Principal Investigators
Dr. W. Marston Linehan and Dr. Ramaprasad Srinivasan (Lead Investigator), NCI Center for Cancer Research

Why This Trial Is Important
Renal cell carcinoma (RCC), the most common type of kidney cancer, often stimulates the growth of a large supply of new blood vessels (angiogenesis) to provide the oxygen and nutrients needed for continued tumor growth. Two drugs recently approved by the U.S. Food and Drug Administration for the treatment of patients with RCC, sorafenib (Nexavar) and sunitinib (Sutent), work by disrupting the angiogenesis process. However, RCC tumors often develop resistance to these drugs.

A new drug called vandetanib (Zactima) also inhibits angiogenesis by interfering with a protein involved in the process: vascular endothelial growth factor receptor 2 (VEGFR2). In addition, vandetanib also inhibits epidermal growth factor receptor (EGFR), a protein that mediates several functions essential for tumor cell growth. Clear cell RCC "is characterized by mutations in a gene we identified that is called the VHL gene," explained Dr. Linehan. "VHL regulates a number of things, including angiogenesis. Vandetanib targets two important parts of the VHL gene pathway - VEGFR2 and EGFR."

In this randomized trial, patients who have RCC that cannot be surgically removed (unresectable) or that has spread (metastatic) and who have previously received sorafenib or sunitinib will take vandetanib daily until their disease progresses or they develop unacceptable side effects.

In addition to monitoring the patients' tumors, the researchers will perform magnetic resonance imaging scans to visualize how vandetanib affects the blood supply to the tumors. The researchers will also collect blood samples from all participants to see if vandetanib is affecting the targeted proteins in the VHL gene pathway.

"We spent 10 years identifying this gene here at NCI, so we're thrilled to be conducting this trial targeting the VHL pathway," said Dr. Linehan.

For More Information
See the lists of entry criteria and trial contact information at http://www.cancer.gov/clinicaltrials/NCI-08-C-0039 or call the NCI's Clinical Trials Referral Office at 1-888-NCI-1937. The toll-free call is confidential.