A Phase 1 clinical trial is underway at Nebraska Medical Center, investigating the combination of abexinostat, a targeted therapy, with temozolomide for patients with recurrent high-grade glioma. The study, which began in 2023, seeks to determine the maximum tolerated dose of abexinostat alongside a standard dose of temozolomide, while also evaluating the efficacy of the combination in shrinking recurrent grade 3 and 4 gliomas.
Targeted Approach to Glioma Treatment
According to Dr. Nicole Shonka, medical neuro-oncologist and the study’s principal investigator, the trial employs a stepped approach across three dose levels to identify the optimal dosage. Abexinostat, an HDAC inhibitor, stands out by targeting specific HDACs upregulated in glioblastoma, offering a more precise approach compared to broad-spectrum HDAC inhibitors. "This drug better matches the tumor’s molecular signature rather than just across-the-board suppressing all of the HDACs," Dr. Shonka explained.
Potential Benefits and Risks
The combination therapy presents potential risks, including impacts on blood counts, with temozolomide primarily affecting platelets and abexinostat affecting white blood cells. Other potential side effects include constipation from temozolomide and changes in blood electrolytes from abexinostat. However, the targeted nature of abexinostat may lead to fewer overall side effects compared to traditional chemotherapies. "Targeted therapies add the benefit of attacking specific things," Dr. Shonka noted. "You don't have the same kinds of toxicities, and hopefully, you don't have the same long-term detrimental side effects."
Future Directions
If the results are promising, Dr. Shonka envisions expanding the research into a larger clinical trial and potentially using the combination therapy for newly diagnosed patients. The fact that abexinostat has already been studied in lymphoma patients could potentially accelerate its development for glioma treatment. "There is the ability to fast-track it," Dr. Shonka said. "It's already developed, and it's something that could quickly be made available."
The trial aims to enroll between nine and 18 patients and is registered under Clinicaltrials.gov identifier NCT05698524.
