CLEVELAND – The National Institutes of Health has awarded $800,000 for a novel clinical trial, led by researchers at University Hospitals (UH) Case Medical Center, testing a drug that targets stem cells of glioblastoma multiforme (GBM), the most common and aggressive type of brain cancer. Funded though the NIH’s 2009 American Recovery and Reinvestment Act stimulus package, the multi-center national study is coordinated through the Adult Brain Tumor Consortium.
GBM, which is notorious for growing back within months of surgery, is the type of cancer that recently killed Sen. Edward Kennedy. GBM stem cells, which are resistant to radiation and chemotherapy, are believed to be the reason that these tumors recur even after complete surgical removal.
Charles Nock, M.D., of the UH Ireland Cancer Center, is the principal investigator (PI) of this study. He and Andrew Sloan, M.D., co-PI, Peter D. Cristal Chair of Neurosurgical Oncology, and Director of the Brain Tumor and Neuro-oncology Center in the UH Neurological Institute, will lead the study of the drug, GDC-0449, developed by Genentech. The drug seeks to block a cellular molecular pathway, known as the sonic hedgehog pathway, that is crucial to the maintenance of these stem cells, known to be present in aggressive brain tumors.
“We believe that there is a small population of these stem cells that are the driving force in the development of several types of cancer, including glioblastoma multiforme,” said Dr. Nock, who is also Assistant Professor of Medicine at Case Western Reserve University School of Medicine. “We have evidence from laboratory studies that GBMs have these stem cells, and we also have evidence that says this drug works against stem cells like this.”
Recently published studies from other medical centers in the New England Journal of Medicine and Science showed that this drug had positive results in treating medulloblastoma, a brain tumor more prominent in children, as well as basal cell carcinoma.
According to Dr. Sloan, doctors have been targeting glioblastoma tumor cells with surgery, chemotherapy, and radiation, but have only made incremental increases in median survival time. GBMs typically recur following surgery in about six months and survival time is about 15 months. One explanation is that these tumor stem cells may linger in the brain and aggressively reform into tumors.
“This a new way of thinking about brain tumors that might explain why we’ve had such difficulty controlling them for the past 30 years,” said Dr. Sloan, who is also Associate Professor of Neurological Surgery at Case Western Reserve University School of Medicine. “We hope these new targets will now work to eradicate the cancer.”
The trial will enroll 40 patients nationwide. Half of the patients will receive the drug prior to surgery and half will not. Following surgical removal of the brain tumor, all the patients will then receive the drug.
“By giving the drug to half the patients before surgery, we can assess changes in pathway activity at the cellular level, and if that causes changes in the tumor,” said Dr. Nock.
According to Dr. Nock, for the stimulus funds, the government was looking for a few, very promising trials asking unique scientific questions. “Fortunately, we were one of the projects to be selected,” he said.
UH has a track record for stem cell research and is a founder of the National Center for Regenerative Medicine. According to the doctors, UH Case Medical Center was well positioned for this proposal. Dr. Sloan’s laboratory has been researching the sonic hedgehog pathway for about a year. He saw the potential of the new drug and was able to partner with Dr. Nock, a clinical researcher, to formulate this clinical trial.
Dr. Nock called this an excellent example of the multidisciplinary team approach that is stressed at UH Ireland Cancer Center. And added, Dr. Sloan, “With the biological sophistication and interdisciplinary support that is on this campus, we were able to put together a proposal that is exciting, clinical relevant, and has the potential to dramatically change the field if our hypothesis is correct.”
Enrollment in the study will begin at various times this fall depending on the location of the study site. In Cleveland, the study is expected to open in late 2009.