An Exceptional Cancer Centerby Anna Williams | photography by LAURA BROWN and JIM PRISCHING
The Lurie Cancer Center solidifies its place among the country’s elite after extraordinary growth and a top rating from the National Cancer Institute.
Newly diagnosed with malignant glioblastoma, Harold “Woody” Wolff was looking for his best chance at beating this aggressive and deadliest of brain cancers. He received that chance — and much more — after seeking a second opinion from James Chandler, MD, ’96 GME, the Lavin/Fates Professor of Neurological Surgery and co-director of the Lou and Jean Malnati Brain Tumor Institute at Northwestern Medicine.
This spring, Wolff became the first patient in a first-of-a-kind clinical trial testing a neural stem cell therapy that works with a common cold virus to attack cancer cells deep within the brain. Unlike most clinical studies for brain cancer that often come into play after tumor recurrence — the hallmark of gliomas — this trial, known as NU-16CO4, focuses on treating and attempting to cure the disease upfront.
Above: After Wolff’s brain tumor was surgically removed, Northwestern Medicine neurosurgeons injected a concoction of neural stem cells loaded with virus into his brain to attack remaining cancer cells typically resistant to chemotherapy and radiation. Wolff’s dose of the new drug is pictured.
A green light from the Food and Drug Administration (FDA) for a new, untried therapeutic approach never comes without numerous biological studies and exacting data collection and analysis to ensure a minimum baseline of safety. While the preclinical work conducted by principal investigator Maciej “Matt” Lesniak, MD, the Michael J. Marchese Professor and chair of Neurological Surgery, demonstrated that the novel drug works when injected into the brains of animal models, investigators must try the therapy in humans to find out if it will improve patient outcomes.
The fact that no one knew exactly what would happen and what side effects might develop, from brain swelling to death, didn’t deter Wolff from participating in the phase I trial. He and his family only saw a promising avenue for help and hope in overcoming this lethal disease.
“Well, someone had to be first,” says this 64-year-old resident of St. Charles, Illinois. “I was willing to be that person.”
Harold Wolff, below with his family pre-surgery. Wolff was the first patient to try the new treatment for glioblastoma.
Short-term memory loss. Difficulty retrieving words. Wolff began noticing these problems in early April while at work and home, making his family concerned about his brain health. “Because of a family history, our first reaction was that he had early-onset Alzheimer’s disease, and he should get checked out,” recalls Wolff’s daughter, Jaclyn Youngquist. “But my dad doesn’t always go to the doctor when he should.”
Later that month, though, Wolff, owner and president of a water and waste water management services company based in Elgin, found himself tongue tied while giving a presentation in Salt Lake City to clients. His colleagues had to take over. Upon returning home, Wolff immediately went to the emergency room at Northwestern Medicine’s Delnor Hospital in Geneva. An MRI scan of his brain showed a large mass. “I asked what that meant,” Wolff recalls. “They said, ‘You have a very large brain tumor,’ and then they kept me in the hospital for several days.”
After making the initial diagnosis, John Brayton, ’90 MD, a neurosurgeon at Delnor, and his team referred Wolff to the Malnati Brain Tumor Institute, which is part of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and located at Northwestern Memorial Hospital. Chandler got the seal of approval from one of Wolff’s distant relatives — a spine specialist who knew of the skilled neurosurgeon. “After doing a lot of research, it made sense to find the best doctors as close to home as possible,” Youngquist says. “Northwestern has a great reputation.”
Today’s standard treatment for malignant glioma follows three steps: surgery, radiation and chemotherapy. During the past 15 years, significant advances in these therapies have failed to raise the survival rate for malignant glioma beyond two years. “That’s just not good enough,” says neuro-oncologist Roger Stupp, MD, co-investigator on the trial and co-director of the Malnati Brain Tumor Institute, a post he assumed upon joining Northwestern Medicine this spring.
In 2005, Stupp demonstrated that chemotherapy with the drug temozolomide in conjunction with radiotherapy increased survival for patients with glioblastoma. Known as the “Stupp Protocol,” this has become the standard of care around the world and is an important component of the new neural stem cell therapy trial.
Intended to test the safety and dosage of the treatment, the first phase of clinical trial NU-16CO4 involves injecting neural stem cells loaded with virus throughout the brain cavity at the time the initial tumor is surgically removed. For Wolff’s May 5th surgery, Chandler and Lesniak worked in the operating room together: The former performed the two-hour tumor resection and the latter the 10-minute experimental procedure. Wolff recovered well from both interventions without a hitch.
“It was extremely thrilling to see an idea that I had in the laboratory a dozen years ago and developed through 10 years of publications and $20 million of government-funded studies finally come to fruition,” says Lesniak about the clinical trial’s inaugural patient. “Of course, I was also happy that Mr. Wolff didn’t experience any adverse side effects.”
Well, someone had to be first. I was willing to be that person.
After brain surgery, glioblastoma patients typically wait three to six weeks before starting radiation and chemotherapy to ensure wound healing and that they are healthy enough for further treatment. However, a unique aspect of the investigational drug called for a faster timeline. Preclinical data had indicated that radiotherapy could synergistically accelerate and boost viral replication of the engineered adenovirus and its cancer killing properties.
“With this trial, we wanted to start radiation therapy sooner rather than later,” says co-investigator Sean Sachdev, MD, ’16 GME, assistant professor of Radiation Oncology. For Wolff and the other two clinical trial patients who have followed him this summer, optimizing the potency of the investigational drug meant starting radiotherapy no later than 10 days after surgery.
Neurosurgeon Maciej “Matt” Lesniak, MD (bottom left), during Wolff’s procedure. Above, colleagues Angela Bohnen, MD, and James Chandler, MD, ’96 GME, with Lesniak in the operating room.
Advancements in medicine come from pushing the boundaries of care to offer the best options, especially when there are few on hand, as in the case of malignant glioma. Participants in clinical trials are as much pioneers as the clinicians and scientists who translate discoveries from the bench to the bedside. Says Lesniak, “While he fit all the eligibility criteria, most importantly, Mr. Wolff was not afraid to be the first in the world to undergo a treatment that could cause as much harm as good.”
Since completing his cancer treatments, Wolff has been able to go back to work and spend time with friends and family. He continues to maintain a positive outlook on his prognosis. “I thought it was worth a chance,” he says of his participation in the trial. “Hopefully it will work for me and others, and we can live free of cancer for many more years to come.”
Visit cancer.northwestern.edu or call 312-695-1102 if you or someone you know would like to get involved in a clinical trial for cancer at Northwestern.
NORTHWESTERN DEVELOPS TWO NEW INVESTIGATIONAL DRUGS
NU-16CO4 is the second drug developed at Northwestern in pre-clinical research to get authorized by the FDA as an investigational new drug, a complex process that involved a multidisciplinary team of 40 people and 25 offices at Northwestern to set up.
The first drug, NU-0129, combats glioblastoma using spherical nucleic acids to target a gene overexpressed in the cancer, BCL2L12. It’s the result of a collaboration between the laboratories of Alexander Stegh, PhD, assistant professor of Neurology in the Division of Neuro-oncology and of Medicine, and Chad Mirkin, PhD, the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, a professor of Medicine in the Division of Hematology and Oncology and director of Northwestern’s International Institute for Nanotechnology.
The early-stage clinical trial for NU-0129, led by Priya Kumthekar, MD, ’11, ’12 GME, assistant professor of Neurology in Neuro-oncology and of Medicine in Hematology and Oncology, will investigate whether the drug is capable of crossing the blood-brain barrier to reach brain tumors in people.
Stegh, Mirkin, Kumthekar, Chandler, Lesniak and Stupp are all members of the Lurie Cancer Center.