CTRC researcher receives special $1.62 million orphan disease grant from FDA

University of Texas Health Science Center at San AntonioOct 5 2014

A researcher at the Cancer Therapy & Research Center is the leader on a study receiving a special $1.62 million orphan disease grant from the Food & Drug Administration.

The FDA's four-year grant will allow Andrew Brenner, M.D., Ph.D. to continue the study how the drug TH-302 may help people with devastating brain tumors called glioblastomas. The money will fund Phase II clinical trials for patients, as well as some supporting studies such as PET imaging to try to predict which patients will benefit most from this drug.

"We've seen preliminary evidence of benefit in patients with glioblastoma whose tumors have grown despite the use of Avastin. By that stage it is a horrible disease with a median survival of about four months," said Dr. Brenner, a CTRC neuro-oncologist. "The fact that TH-302 has shown evidence of helping keep some people alive means we need to do a larger study to see if this holds up and really makes a difference for patients with glioblastoma."

The FDA is charged with helping to develop drugs for diseases that are not widespread, and therefore not as likely to receive private investment by pharmaceutical companies.

Glioblastoma, while devastating, is not common and so is considered an orphan disease. Threshold Pharmaceuticals, the company that developed the drug, is supplying it for the clinical trial. Also participating in the study will be Dana-Farber Cancer Institute and UT Austin.

Brain tumors called glioblastomas grow so fast they have to create their own blood supply to deliver themselves enough oxygen. They do this through a sort of biological ballet: the aggressive growth activity sucks down the oxygen level around the tumor, creating a low-oxygen or hypoxic state. Hypoxia stimulates the tumor cells to make a substance called VEGF, which stimulates development of more blood vessels that in turn feed the tumor.

The drug Avastin knocks out VEGF, inhibiting vascular growth. By doing that it keeps the oxygen level in the tumor area down. The result is a slowing of the tumor's growth, Dr. Brenner said, but that slowdown is temporary, because the tumor responds by growing toward a more oxygen-rich area, much the way a plant grows toward light.

This study combines Avastin with TH-302, which attacks cells in a low-oxygen environment. The Avastin basically creates the arena where the TH-302 does its best work, sparing the body's healthier cells. "So you don't hurt the bone marrow and the kidneys and the liver and other areas" that often suffer in chemotherapy treatments, Dr. Brenner said.