![Drs. Desai and Wise-Draper stand and smile on a bridge in UC's CARE/Crawley Building](https://www.uc.edu/news/articles/2024/02/n21229373/jcr:content/image.img.cq5dam.thumbnail.500.500.jpg/1711461944297.jpg)
Collaborative University of Cincinnati Cancer Center team opens Phase 2 brain tumor trial
Falk Catalyst Award funds next phase of research seeking new treatments for glioblastomas
A multidisciplinary team of University of Cincinnati Cancer Center researchers have opened a Phase 2 clinical trial to test a new combination treatment for glioblastomas (GBM), the most deadly form of brain tumors.
The team, led by UC’s Pankaj Desai, PhD, and Trisha Wise-Draper, MD, PhD, has been awarded a Catalyst Research Award from the Dr. Ralph and Marian Falk Medical Research Trust to move the trial forward.
Study background
Difficult to diagnose at early stages, GBMs are aggressive brain tumors that become symptomatic once the tumor is substantial. Current treatments include immediate surgery to safely remove as much tumor as possible, radiation and chemotherapy, but the tumor often recurs or becomes resistant to treatments. The average patient survives no more than 15 months after diagnosis.
Drug-based treatments for GBMs face an additional challenge known as the blood-brain barrier, which only allows certain compounds into the brain based on their physical and chemical properties.
The research team is focused on the use of a drug called letrozole that has been used for more than 20 years as a treatment for breast cancer. The drug targets an enzyme called aromatase that is present in the breast cancer cells and helps the cells grow.
Early research in Desai’s lab found that aromatase was present in brain tumor cells, making letrozole a potential new treatment for GBMs.
The team is testing the drug letrozole as a treatment for glioblastoma, a deadly and aggressive brain tumor. Photo/National Cancer Institute.
Phase 0/1 trial results
To bring letrozole from Desai’s lab to patients’ bedsides, he collaborated with Wise-Draper and neuro-oncologists and neurosurgeons at UC’s Brain Tumor Center to launch a Phase 0/1 clinical trial.
“In the academic setting, we are very good at doing molecular research that enhances our understanding of the mechanism of disease and preclinical characterization of efficacy, safety and other aspects of drug development research,” said Desai, professor and chair of the Pharmaceutical Sciences Division and director of the drug development graduate program in UC’s James L. Winkle College of Pharmacy. “But you can’t translate this into a clinical trial without a Phase 1 clinical trial expert like Dr. Wise-Draper and the experts at the Brain Tumor Center.”
The researchers published the results of the Phase 0/1 trial March 26 in Clinical Cancer Research, a journal of the American Association for Cancer Research.
Pankaj Desai, PhD. Photo/Andrew Higley/UC Marketing + Brand.
“Letrozole was safe up to the highest dose, and there were no safety concerns in the Phase 0/1 trial,” said Wise-Draper, section head of Medical Oncology and professor in the Division of Hematology/Oncology in UC’s College of Medicine. “The biggest conclusion is that it was safe and that we could reach what we felt was going to be the effective dose based on Dr. Desai’s preclinical work.”
The research team collected tumor tissues from patients enrolled in the Phase 0/1 trial and found that letrozole was crossing the blood-brain barrier when they analyzed the samples in Desai’s lab.
“We can categorically show that in humans the drug actually crosses and reaches the brain tumor at concentrations that we believe are likely to be most efficacious,” Desai said.
Phase 2 trial design
Trisha Wise-Draper, MD, PhD. Photo/Nyla Sauter/University of Cincinnati Cancer Center.
Since GBMs are aggressive and complicated tumors, Desai said most likely new effective treatments will be combinations of drugs instead of one single drug.
In the Phase 2 trial, patients will be given letrozole in combination with a chemotherapy drug called temozolomide that is already approved as a GBM treatment. Desai said preclinical research in his lab and input from Brain Tumor Center collaborators, including neuro-oncologist and former UC faculty member Soma Sengupta, suggested this combination treatment could be more effective than letrozole alone.
A total of 19 patients with recurrent GBM who are no longer eligible for additional surgery will be enrolled in the first stage of the trial. The results from this trial will guide the design of future larger Phase 2 trials.
The team estimates it will complete enrollment within two years, and two patients have already been enrolled.
Collaboration and funding support
Wise-Draper and Desai have worked together on various research projects for nearly 15 years and said this project would not be moving forward without the varied expertise each team member brings.
“I think collaboration with multidisciplinary teams is critical to be able to have the expertise and all the components you need, including biostatistics, pharmacokinetics, clinical, basic science and neuro-oncology expertise,” Wise-Draper said. “The future of all science is team science. No one really can do everything on their own anymore because we’re all too specialized.”
“Only academic centers with integrated scientific and clinical expertise are able to move their molecules from the research bench to clinical trials,” Desai added. “It takes a lot of persistence, ups and downs, highs and lows of funding, but we have been supported by a very strong team of people. It’s a journey that has taken a while and a lot of hard work by a number of people, and we’re in a very exciting stage.”
Early-stage support for the preclinical and clinical trial studies was provided by the UC Brain Tumor Center, where investigators from UC’s colleges of Medicine, Pharmacy, Engineering and Applied Science and Cincinnati Children’s Hospital collaborate on brain tumor research.
UC’s Brain Tumor Center provided direct support for the completion of the Phase 0/1 trial and some of the correlative mechanistic studies that will continue during the Phase 2 trials using funds raised in the annual Walk Ahead for a Brain Tumor Discoveries fundraiser.
The Falk Catalyst Award provides up to $350,000 in seed funding to support translational research projects, which the researchers said was crucial in opening the new trial.
“Oftentimes the funding is somewhat limited for initial clinical trial development compared to many other more early-stage studies that you can do,” Desai said. “So that gap is filled by foundations like the Falk Medical Research Trust, and that really is very helpful and plays a critical role in accelerating clinical development.”
“It would not be possible if we didn’t have the funding to be able to bring this combination into patients that desperately need new treatment options,” Wise-Draper said.
As the clinical trial progresses, the team is also collaborating to find other drugs to combine with letrozole to treat GBMs, funded by a $1.19 million National Institutes of Health/National Institute of Neurological Disorders and Stroke grant. The team is already preparing a proposal for larger confirmatory Phase 2 studies and expanding the opportunities for cutting-edge brain tumor clinical trials in Cincinnati.
Desai said the ongoing research includes additional collaboration from experts including David Plas, PhD, Biplab DasGupta, PhD, and Tim Phoenix, PhD (molecular/cancer biology); Gary Gudelsky, PhD (neuro-pharmacology) Rekha Chaudhary, MD, and Lalanthica Yogendran, MD (neuro-oncology); Mario Medvedovic, PhD (bioinformatics and genomics); and Shesh Rai, PhD (biostatistics). Many graduate students, postdoctoral fellows and the clinical trials support staff also provide essential support for the project.
Impact Lives Here
The University of Cincinnati is leading public urban universities into a new era of innovation and impact. Our faculty, staff and students are saving lives, changing outcomes and bending the future in our city's direction. Next Lives Here.
For more information on the trial, please call 513-584-7698 or email cancer@uchealth.com.
The team also recently published research in the International Journal of Molecular Sciences reviewing approaches to overcome treatment resistance to temozolomide to treat GBMs.
Featured photo at top of Drs. Desai and Wise-Draper. Photo/Nyla Sauter/University of Cincinnati Cancer Center.
Related Stories
Cincinnati researchers want to know if MRIs can work better
June 28, 2024
![WVXU logo](/content/dam/refresh/uc-news/news-icons/dark/wvxu.png)
WVXU and the Cincinnati Business Courier highlighted a new collaboration between the University of Cincinnati College of Medicine, UC Health GE HealthCare, JobsOhio, REDI Cincinnati and Cincinnati Children’s to create an MRI Research and Development Center of Excellence located on UC’s medical campus.
UC opens Blood Cancer Healing Center
June 28, 2024
![WLWT 5 logo](/content/dam/refresh/uc-news/news-icons/dark/wlwt-dark.png)
Media outlets including WLWT, Local 12, Spectrum News, the Cincinnati Enquirer and Cleveland.com highlighted the opening of the University of Cincinnati Cancer Center's Blood Cancer Healing Center.
New project aims to better support teen mothers in Adams County
June 27, 2024
![WCPO logo](/content/dam/refresh/uc-news/news-icons/dark/wcpo-dark.png)
WCPO highlighted a partnership between the University of Cincinnati and the Adams County Health Department that is aiming to provide better support for teen mothers in the county.
Free Wi-Fi, work area coming to Greater Cincinnati
June 27, 2024
![Local 12 logo](/content/dam/refresh/uc-news/news-icons/dark/wkrc-logo-dark.png)
St. Lawrence Park in Price Hill now has free Wi-Fi and a furnished outdoor space for community members to access digital needs. The space is part of The Nodes Project, which stands for “Neighborhoods of Design Engagement": a collaboration between UC DAAP communication designers and community entities.
Study aimed at reducing opioid overdose deaths presents results
June 27, 2024
![Spectrum News logo](/content/dam/refresh/uc-news/news-icons/dark/spectrum-news.png)
The University of Cincinnati's John Winhusen and Caroline Freiermuth discussed the evidence-based practices implemented during the HEALing Communities Study to fight the opioid epidemic with Spectrum News.
University of Cincinnati, UC Health collaborate with GE HealthCare on MRI research center
June 26, 2024
The University of Cincinnati and UC Health are collaborating with GE HealthCare, JobsOhio, REDI Cincinnati and Cincinnati Children’s to create an MRI Research and Development Center of Excellence located on UC’s medical campus.
The health impact of living near a natural gas leak
June 25, 2024
![BBC logo](/content/dam/refresh/uc-news/news-icons/dark/bbc.png)
UC College of Arts and Sciences Professor Amy Townsend-Small talks to the BBC about the health issues faced by neighbors of leaking natural gas wells.
Male birth control gel inches towards FDA approval
June 25, 2024
![Yahoo News logo](/content/dam/refresh/uc-news/news-icons/dark/yahoo.png)
The University of Cincinnati's Wesley Baas spoke with Yahoo News and the Cincinnati Enquirer about a new male birth control gel that could be close to receiving FDA approval.
University of Cincinnati Cancer Center launches Blood Cancer Healing Center
June 25, 2024
The University of Cincinnati Cancer Center celebrated the opening of its state-of-the-art Blood Cancer Healing Center June 24.
Carnegie Foundation recognizes UC with Leadership for Public Purpose classification
June 24, 2024
UC part of inaugural group honored for focusing on developing students as leaders