Pancreatic cancer outcomes, even for patients diagnosed with early-stage disease, have remained bleak because the disease often recurs quickly and metastasizes to other locations. Treatment plans require a proactive approach, often testing novel therapies within a clinical trials setting. “Clinical trials help us find new, potentially impactful treatments that can also benefit patients today,” says Daniel P. Nussbaum, MD, surgical oncologist. “We’re growing our clinical trial portfolio with studies uniquely tailored to improve cure rates for the most diverse patients.”

In just three years, Duke’s clinical trial participation for patients with localized pancreatic cancer grew to almost 20%. Next year, the team aims to achieve at least 25%, and in five years, their goal is for at least 50% of patients to receive treatment that is only available as part of a clinical trial. This has been a collaborative effort between surgical oncology, medical oncology, and radiation oncology disciplines, as well as colleagues in gastroenterology and interventional radiology.

Currently, the team leads three innovative protocols for patients with localized pancreatic cancer, with several others under development and expected to open later this year. Recognizing that patients often come to Duke from a distance, the team has prioritized protocols that may let patients receive their standard chemotherapy locally to limit the travel burden to patients and allow patients to continue treatment with their current oncologists. 

The first trial tests if a single dose of chemotherapy delivered directly to the liver one week before surgical resection can prevent or delay liver metastasis. “Liver metastases drive survival outcomes in most patients with pancreatic cancer. It’s the most common site for metastatic spread or recurrence, and patients who develop liver metastases have worse survival outcomes than those who develop spread to other sites, such as the lungs,” says Nussbaum. This trial is one example of the team’s collaboration — Nussbaum and Niharika B. Mettu, MD, PhD, gastrointestinal medical oncologist, work with interventional radiologists to dose and administer the chemotherapeutic agent before surgery. 

The second is a multisite trial based on promising phase I results from Memorial Sloan Kettering, which tests if a personalized mRNA vaccine prevents recurrence following surgery. In the phase I trial, 50% of patients given the vaccine experienced a robust immune response, and none of the patients demonstrating this response had recurrence at 18 months. Now being tested at the highest level as a randomized trial, “this is one of the most exciting studies in pancreatic cancer right now, and it’s here at Duke,” says Nussbaum. Mettu serves as the co-principal investigator for the study. 

Third, DCI’s Pancreatic Cancer Program built a unique partnership with the National Institutes of Health (NIH) to offer T cell therapy to patients with earlier-stage disease. This is the first time this treatment has been employed in an effort to improve recurrence and cure rates. “The idea is to start intervening earlier in the disease by engaging the patient’s immune system to target their own tumor cells,” says Nussbaum. “This program leverages Duke’s exceptional surgical program and research capabilities with the NIH’s expertise in administering this type of immunotherapy, which they pioneered. It has been made possible by collaboration between the two groups and our regional proximity.”

Mettu adds that the entire Duke team is committed to developing more personalized therapies and testing them within clinical trials. By the end of this year, the team anticipates two new perioperative trials to open testing targeted therapies for patients with specific genomic or molecular features, including those whose tumors overexpress Claudin 18.2 (over 50% of patients) and those whose tumors exhibit loss of the gene MTAP (approximately 20% of patients). 

Another big area of exploration is therapy targeting KRAS in pancreatic cancer because over 90% of pancreatic tumors have mutations in this gene. “We want to explore KRAS-targeted treatments that may suppress this mutation and tumor activity. We have a growing number of trials in our GI and phase I trials program,” says Mettu, director of experimental therapeutics at Duke. These molecularly and genomically targeted trials will offer the possibility of personalized oncology care for patients with pancreatic cancer, which has been a challenge in this disease that is now just becoming possible to overcome. “It’s important to know that there is hope during every stage of a pancreatic cancer journey, which evolves throughout treatment. Hope pervades everything.”