Pancreatic cancer remains one of the most aggressive types of cancer, and patients with unresectable disease have a median overall survival duration of just 1 year, despite treatment with chemotherapy and radiation. Although increasing the radiation dose to the tumor might improve treatment outcomes for such patients, the adverse effects of radiation therapy have made such increases impractical. But now, researchers at The University of Texas MD Anderson Cancer Center are leading a new clinical trial to determine whether a radiomodulating agent will enable targeted radiation therapy to be delivered at high doses to unresectable pancreatic tumors without harming nearby vital structures.
“There is a lot of very important anatomic real estate right around the pancreas. There’s the intestines, the liver, and major blood vessels,” said Cullen Taniguchi, M.D., Ph.D., an assistant professor in the Department of Radiation Oncology. Even with modern modalities such as stereotactic body radiation therapy (SBRT), which allows the delivery of high doses of focused radiation to tumors while minimizing the dose to nearby organs, oncologists have not been able to deliver high enough radiation doses to substantially delay the progression of pancreatic cancer.
Dr. Taniguchi believes this situation could soon change. He is leading a randomized dose-escalation trial to see whether a bowel-protecting drug, GC4419, will enable SBRT to be delivered safely to the pancreas at higher doses than ever before.
Radiomodulating agent GC4419
The radiomodulating agent GC4419 is a superoxide dismutase mimetic. The drug removes superoxide radicals that are formed during radiation treatment and causes them to become less damaging by converting them to hydrogen peroxide. Normal tissues contain antioxidant enzymes that neutralize hydrogen peroxide, but tumors often do not. Radiation produces superoxide radicals in a dose-dependent fashion. Because SBRT uses higher doses than do other radiation therapy modalities, scientists believe that pairing SBRT with GC4419 could help reduce the toxic effects of SBRT in normal tissues without reducing its tumoricidal benefits.
When GC4419 was tested in patients with head and neck cancer who were receiving radiation therapy, researchers reported a 40% reduction in oral mucositis, a common adverse effect of such therapy. These results led Dr. Taniguchi and colleagues to believe the radiomodulating agent could also improve outcomes for patients with pancreatic cancer.
The trial (No. 2017-0606) is enrolling men and women with locally advanced, unresectable pancreatic cancer and an Eastern Cooperative Oncology Group performance status score of 2 or lower. Patients must have received 3–7 months of standard induction chemotherapy prior to beginning the trial.
Patients are randomly assigned to receive GC4419 or placebo; these are given before each of the five SBRT sessions, which take place on consecutive days. The total radiation doses are escalated using a sequentially adaptive design that accounts for efficacy and toxic effects observed in previous patients.
“The trial is designed to find the highest dose of SBRT that is safe in patients with and without GC4419,” Dr. Taniguchi said. “The underlying hypothesis is that GC4419 will let us get to a higher dose of radiation. We go through three different levels of radiation. The highest dose level will be the highest radiation dose ever given for pancreatic cancer. These are doses we think could substitute for surgery.”
So far, five patients have been enrolled; ultimately the trial will enroll 48. Each patient will be followed up over the course of 3 years, the duration of the clinical trial. The trial’s primary endpoints are toxic effects and the duration of stable disease.
“We’ll know if we’re making a difference because we’ll start seeing patients with disease progression 2 and 3 years later instead of after a year or less,” said Dr. Taniguchi. “Ultimately, we believe these treatments might lead to better outcomes in selected patients.”
For more information, contact Dr. Cullen Taniguchi at 713-792-5131 or firstname.lastname@example.org. To learn more about clinical trials at MD Anderson, visit www.clinicaltrials.org and search by physician, cancer type, or treatment.