Collaborating for Clinical Trial Success
RESEARCHERS AT DUKE HAVE BEEN WORKING for years to harness the power of the body’s immune system to fight brain tumors. Annick Desjardins, MD, FRCPC, says the successes Duke has had so far in developing immunotherapies—treatments that boost the immune system’s ability to kill cancer— are mainly due to strong collaborations.
As a clinical investigator of the clinical trial of a genetically modified version of the poliovirus, PVSRIPO, she worked closely with researchers Matthias Gromeier, MD, and Darell Bigner, MD, Ph.D., meeting weekly. Using what she learned from the brain tumor patients who received the treatment, she could take that information back to Gromeier and Bigner; they could refine the doses until they got it right.
“We were able through our first trial to refine the genetically modified poliovirus as precisely as possible, to make it as effective as possible,” says Desjardins, director of clinical research at the Preston Robert Tisch Brain Tumor Center and an associate professor of neurosurgery and neurology.
The ability to fine-tune the doses is something that Desjardins says was made possible through donor funding. Had she and her colleagues relied solely on support from the National Institutes of Health or other federal grants, they would not have had the same level of freedom to refine the doses. They also would have been limited in the time they could have spent on the research.
In the first phase of the trial, Desjardins and fellow researchers discovered that 21 percent of patients showed significant improvement in long-term survival. Median survival for brain tumor patients at the time of tumor recurrence is six to nine months; typically, less than 5 percent of patients are alive at 36 months, but 21 percent of patients in the trial had a three-year survival rate. “Brain tumor patients are being told today when they’re diagnosed with a brain tumor, ‘Go home. Do your paperwork. You’re going to die,’” Desjardins says. But now, patients are given hope for outcomes that weren’t possible just a few years ago.
“Now I can tell a patient, the treatment I’m giving you today is better than what I gave in 2012,” she says. “There Is now hope that there is now progress for this challenging disease.” The researchers have now started phase 2 of the trial. They have enrolled 120 patients in the multicenter study, including several medical centers and Duke.
Desjardins and her team are also working with Gromeier and Bigner on a new study that combines poliovirus with drugs known to boost the immune system, called checkpoint inhibitors. The researchers hope to answer whether PVSRIPO can be used before the patient receives chemotherapy and whether adding the checkpoint inhibitors can further increase long-term survival.
In another new immunotherapy study, Desjardins and Bigner examine the effectiveness of an immunotoxin called D2C7, which is released by the bacterium pseudomonas. The toxin is typically unable to attach to cancer cells. However, Bigner has added two antibodies to Pseudomonas that can attach to two receptors that are present at high levels in glioblastoma. The antibodies are then able to release the toxin of the bacteria and infect and possibly kill the cancer cells.