Providence Brain and Cancer Experts Begin First-In-World Novel Brain Tumor Vaccine Research Trial
May 05, 2014
PORTLAND, Ore. — Fourteen months. That’s the median life expectancy of someone diagnosed with high-grade glioma, the most common primary brain tumor in adults, even with the current standard of treatment. Providence Cancer Center researchers and a Providence Brain and Spine Institute neurosurgeon believe immunotherapy might change that statistic. They already have enrolled three patients in an Earle A. Chiles Research Institute Phase 1 trial of a new drug that relies on a genetically-modified version of a common bacterium for its success.
The project originated in the laboratory of Providence researcher Keith Bahjat, Ph.D. He has extensive history working with Listeria monocytogenes, a bacterium that in its native form can cause serious illness in individuals with compromised immune systems. Bahjat collaborated with scientists at Aduro BioTech, who have engineered a version of the Listeria bacterium for use as a cancer vaccine. The team added two cancer-specific genes to the Listeria strain, transforming a once harmful bacterium into a vaccine that has the potential to fight cancer. The vaccine, known as ADU-623, is based on Aduro’s propietary Listeria platform that teaches the immune system that these cancer-specific proteins are harmful by displaying them in the context of a bacterial infection. The response to the bacterial infection triggers the activation of immune cells which can now recognize the cancer cells as dangerous.
“By putting the two together, the bacteria and the tumor, we teach the immune cells that this target is bad and needs to be destroyed,” said Marka Crittenden, M.D., Ph.D., director of Translational Radiation Research at the Earle A. Chiles Research Institute and principal investigator of this clinical trial.
Drs. Crittenden and Bahjat, along with Providence Brain and Spine Institute neurosurgeon Pankaj Gore, M.D. and Aduro, developed the protocol and worked through the FDA investigational new drug process in order to open a Phase 1 trial for the vaccine which is designed to use the body’s immune system to find and destroy the remnants of a brain tumor.
“For more than 30 years, our field has made little progress in extending the survival of patients with glioblastoma,” said Dr. Gore, co-medical director, cranial services, Providence Brain and Spine Institute. “I firmly believe that immunotherapy is the new horizon in the treatment of this disorder. This trial has the potential to have a significant impact on the standard course of this disease.”
This project was funded by grants from the Kuni Foundation and the Providence Portland Medical Foundation. The clinical trial is the result of philanthropic donations which are funneled directly into financing the research and testing of new treatments for cancer patients.
The trial is for patients who have completed the standard of care for their brain tumor. The study will test three dose levels of ADU-623. The primary goal of the trial is to demonstrate the safety of the vaccine and to determine the optimal dose. The trial also will evaluate the patient’s immune response to the ADU-623 vaccine, as well as any tumor shrinkage that occurs during treatment.
The study will enroll up to 38 patients.
The diagnosis of glioblastoma multiforme often comes after a person experiences a seizure, or symptoms similar to a stroke, and usually requires biopsy or resection of the tumor by a neurosurgeon.
Essentially, the tumor consists of brain cells that have gone bad; it is composed of supporting cells of the nervous system that begin multiplying without regulation. It spreads with tentacles weaving throughout the brain, making it difficult for neurosurgeons to remove the entire tumor. The standard treatment is surgery, followed by radiation and chemotherapy for about six weeks and then six months of additional chemotherapy.
At that point it becomes watchful waiting. Everyone hopes the tumor stays in remission for as long as possible. “We have a lot of patients whose scans look like their tumor is in remission, but we know that almost 100 percent of them, in the next few months to a year, will have a scan that shows the tumor growing again,” said Dr. Crittenden. “This is an appealing area for immunotherapy. because if we can get the immune system involved in controlling this tumor, we may be able to eliminate those other areas where microscopic residual tumor remains.”
To learn more about this trial, contact Chris Fountain, RN, at 503-215-2691 or go to http://clinicaltrials.gov/show/NCT01967758.