PIONEER Trial: Hope for Patients With Unresectable Pancreatic Cancer

A hard-to-treat disease—mainly due to lack of early symptoms—pancreatic cancer accounts for 3% of cancers in the United States and about 7% of cancer deaths, according to the American Cancer Society. Now, researchers have developed a strategy to make pancreatic cancer more responsive to chemotherapy and radiation.

A clinical trial designed by Cancer Research UK will enroll patients with localized pancreatic cancer whose significant tumor burden eliminates surgery from the list of treatment options. Using chemoradiation, which is a combination of chemotherapy and radiotherapy, along with olaparib (a PARP inhibitor, currently approved for ovarian cancer by the FDA), the researchers hope to shrink the tumors to a size where surgery would once again be an option.

“This is the first time we’re looking at ways to make pancreatic cancer cells more sensitive to radiotherapy," Jeff Evans, chief investigator of the trial at the University of Glasgow, said in a statement. "One way to make pancreatic cancer a more treatable disease is to shrink the tumour enough to make surgery a possibility and we hope to see that happen in this trial."

The initial phase 1 study is small, with plans to recruit 36 patients, and will primarily be a dose-finding endeavor.

The trial design has a multi-pronged approach. Radiotherapy and a few chemotherapy agents cause DNA damage to cells, but cancer cells retain their ability to repair this damaged DNA and survive, which can lead to drug resistance. Olaparib, an inhibitor of PARP-1 (a protein that helps repair DNA damage), can stop this process and resensitize the cells to the DNA-damaging agents to cause cell death, resulting in tumor shrinkage.

Once the researchers have finalized on the best dose of olaparib, the second part of the trial will recruit patients who could possibly have surgery to demonstrate proof-of-concept.