The early-phase clinical trial is based on basic research discoveries made in Jonsson Cancer Center laboratories. UCLA researchers have successfully tested the drug in laboratory and animal models. They hope to translate that benefit into patients in the clinic, said Dr. Charles Sawyers, co-principal investigator for the study and the Jonsson Cancer Center scientist whose basic research resulted in the clinical trial.
UCLA laboratory studies have shown that some patients with prostate cancer have lost PTEN, a tumor-suppressor gene. In some patients who have lost PTEN, a gene called mTOR located downstream in the cell-signaling pathway gets turned on and may be driving the cancer. Sawyers, along with co-principal investigator Dr. Robert Reiter, will test a drug called CCI779, which they believe targets mTOR.
"We discovered that tumors missing PTEN seem to be very responsive to CCI779, and it's very clear at a molecular biology level why," Sawyers said. "When you've lost PTEN, mTOR activity gets turned up and tumors become dependent on it for their growth. So a drug that inhibits mTOR should impact the tumor cells but have no effect on the normal cells."
Armed with his laboratory discoveries, Sawyers proposed the prostate cancer study to Wyeth Pharmaceuticals, and the clinical trial was designed. UCLA's Jonsson Cancer Center is the only West Coast site offering this study. Other sites participating include MD Anderson Cancer Center in Texas and Fox Chase Cancer Center in Philadelphia, Sawyers said.
Because CCI779 targets only what is broken in the cancer cell, it is expected to cause very few side effects, Sawyers said.
UCLA researchers are seeking study volunteers with newly diagnosed prostate cancer who are at high risk for recurrence, meaning they have Gleason scores of 8, 9 or 10 and a PSA level of 20 or greater. Because their cancers are aggressive, these patients generally have a 50 to 70 percent chance of recurrence after surgery, Sawyers said.
The conventional treatment for these patients is radiation therapy with or without hormonal therapy, or surgery. Researchers hope that adding CCI779 to surgery may help reduce the risk of recurrence.
"The cure rate for surgery alone is not that high -- only about 30 and 50 percent of men remain cancer free," Reiter said. "We want to see if this drug targets the signaling pathway that we confirmed in our laboratory studies and provides any extra protection. This is a highly translational study, very scientifically oriented, not a conventional drug company study at all. It is entirely a product of the prostate cancer program here at UCLA's Jonsson Cancer Center."
In the study, CCI779 will be administered to volunteers for eight weeks prior to surgery. The prostate will then be removed and researchers will study tumor sample to determine if the drug hit mTOR, its target. Researchers will follow patients, measuring PSA levels and monitoring for recurrences. If the study is successful, researchers may be able to decrease the number of recurrences expected in this patient population, Reiter said.
Prostate cancer is the most common type of cancer found in American men, other than skin cancer, and is the second leading cause of cancer deaths. About 220,900 new cases of prostate cancer will be diagnosed in the United States in 2003, according to the American Cancer Society. About 28,900 men will die of this disease.
For more information on the prostate cancer study, call 310-825-4415.
UCLA's Jonsson Comprehensive Cancer Center is composed of more than 240 cancer researchers and clinicians engaged in cancer research, prevention, detection, control and education. The center, one of the nation's largest comprehensive cancer centers, is dedicated to promoting cancer research and applying the results to clinical situations. In 2003, the Jonsson Cancer Center was named the best cancer center in the western United States by U.S. News & World Report, a ranking it has held for four consecutive years.
For more information, visit the Jonsson Cancer Center Web site at www.cancer.mednet.ucla.edu.
Kim Irwin, kirwin@mednet.ucla.edu
310-206-2805
Mary Hardin, mhardin@mednet.ucla.edu
310-206-3769