Toward tomorrow's treatments
With the support of a nationally funded grant focused on drug development, two early-career researchers at the UK Markey Cancer Center are spearheading novel clinical trials. Their aim is to make next-generation radiopharmaceutical cancer therapies accessible to patients across Kentucky and the world. And they’re doing it in collaboration with several other high-profile cancer centers across America.
Through Markey’s National Cancer Institute UM1 grant – a highly competitive, nationwide five-year grant awarded to only 11 principal investigators (PIs) and institutions – three clinical trials led by Dr. Zin W. Myint and Dr. Aman Chauhan, both assistant professors of medicine at Markey, were selected to be funded by the National Cancer Institute’s Experimental Therapeutics Clinical Trials Network (ETCTN). The ETCTN employs a collaborative, team-based approach to early-phase clinical trials of NCI Investigational New Drug agents in high-priority areas of unmet cancer treatment needs.
“ETCTN trials are about finding the right drug for the right person based on their cancer’s particular molecular makeup using biomarkers,” said Dr. Susanne M. Arnold, associate director of clinical translation at Markey and institutional PI of the UM1 grant, in partnership with The Ohio State University. “This really is the cutting-edge theme of oncology research today.”
Comprising 40 high-profile cancer centers across the United States, the network funds trials led by clinician scientists at participating sites, and the trials are then conducted by the network sites. This team science approach promotes collaboration among institutions and investigators and significantly broadens the field for data collection and research.
All three of the novel ETCTN trials led by Myint and Chauhan focus on the use of targeted radiopharmaceuticals, “an area that is emerging as a key part of cancer treatment overall,” Arnold said. “Having these novel, cutting-edge trials conducted at UK as well as at other sites across the United States allows patients in Kentucky, who may not be able to travel far, to have access to novel cancer treatments and national research close to home,” Arnold said. “These studies really put Markey on the map.”
Neuroendocrine tumors
Chauhan is leading two of the ETCTN trials — both focused on treating neuroendocrine tumors (NETs) with radiopharmaceutical combination therapy.
“Neuroendocrine cancer does not have a whole lot of therapeutic options, as it is somewhat of a rare cancer,” Chauhan said. “However, we’ve seen a sixfold increase in the incidence of neuroendocrine cancer in the last four decades. But the treatment options have not moved at the same pace.”
ETCTN 10388 is a phase I trial investigating the side effects and best dose of triapine – a ribonucleotide reductase inhibitor – plus the radiopharmaceutical lutetium Lu 177 dotatate (lutathera) for the treatment of neuroendocrine tumors. Chauhan hypothesizes that these two agents will work together by stopping the growth of tumor cells while carrying radiation directly to tumor cells without harming normal cells.
Similarly, the ETCTN 10450 phase I trial will examine the combination of Lutathera and the novel DNA-PK inhibitor peposertib for the treatment of neuroendocrine tumors. Targeted radiopharmaceuticals treat cancers by causing DNA damage in tumor cells; however, tumor cells often bounce back by repairing their DNA. Chauhan and his research team are analyzing whether peposertib will improve the efficacy of targeted radiation-based therapy by preventing DNA repair, leading to an overall improvement in treatment outcomes for patients.
Prostate cancer
Led by Myint, the third ETCTN trial (10437) is investigating the use of Sn-117m-DTPA for the treatment of castration-resistant prostate cancer with bone metastases. This novel radiopharmaceutical not only targets cancer in the bone but also minimizes radiation toxicity to patients’ bone marrow – an important consideration for prostate cancer patients who may already have suppressed bone marrow due to previous chemotherapy and/or hormone therapies.
“When prostate cancer metastasizes, it goes to the bone 80 percent of the time, and bone pain is often the presenting symptom,” Myint said. “So this clinical trial is very important for prostate cancer patients.”
