One-two punch for brain tumors? New clinical trial opens

The experimental approach, based on U-M research, delivers two different genes directly into the brains of patients following the operation to remove the bulk of their tumors.

The idea: trigger immune activity within the brain itself to kill remaining tumor cells -- the ones neurosurgeons can't take out, which make this type of tumor so dangerous.

It's the first time this gene therapy approach is being tried in humans, after more than a decade of research in experimental models.

One of the genes is designed to kill tumor cells directly, and is turned on when the patient takes a certain drug. The other gene spurs the body's own immune system to attack remaining cancer cells. Both are delivered into brain cells via a harmless virus.

The Phase I clinical trial has already enrolled two patients who have tolerated the gene delivery without complications. All patients in the study must have a presumptive diagnosis of WHO grade 3 or 4 malignant primary glioma, such as glioblastoma multiforme; patients must not have been treated yet by any therapy. They must also meet other criteria for inclusion in the trial.

More patients will be able to enroll at a pace of about one every three weeks, through a careful selection process. In addition to surgery and gene therapy at U-M, each will receive standard chemotherapy and radiation therapy as well as follow-up assessments for up to two years.

"We're very pleased to see our years of research lead to a clinical trial, because based on our prior work we believe this combination of cell-killing and immune-stimulating approaches holds important promise," says principal investigator Pedro Lowenstein, M.D., Ph.D., the U-M Medical School Department of Neurosurgery professor who has co-led the basic research effort to develop and test the strategy.

Co-leader Maria Castro, Ph.D., notes that the patients who agree to take part in the Phase I trial will be the first in the world to help establish the safety of the approach in humans. "Without them, and without our partners on the U-M Neurosurgery team, and donors to the Phase One Foundation that support our work, we wouldn't be able to take this important step in testing this novel therapeutic approach."

For more about the trial, visit http://umhealth.me/gliomatrial or call 1-800-865-1125.