Study of potential cancer treatment begins at UW

The UW Comprehensive Cancer Center (UWCCC) Tuesday, Nov. 23 received official approval to begin a clinical trial of the first human test of endostatin, a naturally occurring protein and potentially promising cancer treatment that has been shown to cut off the blood supply to tumors in mice.

Related Web sites: Frequently asked questions about the Endostatin Phase I clinical trial UW Comprehensive Cancer Center National Cancer Institute’s Cancer Trials Web site

Chosen as a study site last March by the National Cancer Institute, the UW Comprehensive Cancer Center follows the Dana-Farber/Partners Cancer Care in Boston and the MD Anderson Cancer Center in Houston as the third and final site to announce that its trial is underway.

“Participating in this cancer treatment study is an honor and exciting privilege for the UW Comprehensive Cancer Center,” said George Wilding, professor of medicine at the UW Medical School and principal investigator of the UWCCC’s Experimental Therapeutics Program. “Nothing would make us happier than to find a potentially revolutionary form of cancer treatment in humans. At the same time, we cannot overstate how often that humans have failed to respond to treatments that have shown promising results in animals.”

Wilding also noted that the scope of this study, known as a Phase One clinical trial, is limited to finding a safe dosage for humans, not determining effectiveness as a cancer treatment. Treatment effectiveness would be examined in Phase Two and Phase Three trials, if they occur, and would not begin for one to two years.

In concert with standard Phase One clinical trial procedures at the UW Comprehensive Cancer Center, patients for the UW’s endostatin study will be selected from a pool of cancer patients who have: (1) already been treated by or referred to a medical oncologist at the UWCCC; (2) advanced solid tumors (not leukemia or myeloma) for which no known beneficial therapy exists; and (3) have a cancerous tumor that is easily accessible to repeated biopsies.

The identity of patients who are selected to participate in the UWCCC’s Phase One endostatin study will be kept confidential.

“We will be contacting patients already on our records who represent the best candidates we know of from a scientific perspective and who are willing to make what is clearly a very substantial time commitment.” Wilding said. “We expect to begin giving treatment to the first group of patients the week of December 13.”

Individuals who have contacted the UWCCC’s Cancer Connect service about endostatin over the last several months have received a letter advising them of the selection process described in this news release. Patients who do not meet the UWCCC’s endostatin study criteria are encouraged to contact the UWCCC’s Cancer Connect Service at (800) 622-8922 for information about other clinical trials that may be beneficial.

Because endostatin has never been tested in humans before, the Phase One trials will be limited to a small number of people. Typically, this will range from 15 to 30 patients at each of the three sites.

Once the UWCCC begins giving the drug to patients, three patients will receive endostatin intravenously every day. If no toxic effects are found after four weeks of treatment, another set of six patients will be given a higher dosage. This process will continue with groups of six patients until a maximum safe dosage level is determined. All patients will be carefully monitored through a variety of complex tests.

Endostatin’s potential value as a cancer treatment received considerable attention after a May 1998 New York Times article described early results in mice in the laboratory of Judah Folkman of Harvard Medical School. In these animal studies, endostatin inhibited the growth of existing tumors and caused some to shrink to microscopic lesions. When researchers examined these tiny lesions, they found that the endostatin had blocked the growth of blood vessels that nourished the tumors.

James Thomas, assistant professor of medicine at the UW Medical School and chair of the UWCCC’s endostatin study, said that endostatin is one of several potential cancer treatments known as angiogenesis inhibitors – drugs that halt the creation of blood vessels that keep tumors alive.

“If endostatin is effective, it would represent a whole new approach in cancer treatment,” Thomas said. “Instead of killing the cancer cells, which we typically do with chemotherapy or radiation, we want to know if cutting off a tumor’s blood supply represents a form of treatment that might prevent the spread of cancer without the toxicity associated with existing radiation or chemotheraphy treatments.”

More information about the UWCCC’s endostatin study is available by contacting the UWCCC’s Phase One Program at (608) 262-8330 or the UWCCC’s Cancer Connect service at (800) 622-8922. Those with Internet access will find more information on the UWCCC’s Web site at http://www.cancer.wisc.edu/news/news17.html.

General information about clinical trials can be found on the National Cancer Institute’s Web site at http://cancertrials.nci.nih.gov/