Pancreatic Cancer Trial Platform Poised to Lead to Quicker, More Efficient Research

Vincent J. Picozzi Jr, MD

Due to the prevalence, low survival rates, and complexity of the disease, there is an unmet need for novel therapies in pancreatic cancer with a quicker turnaround, according to Vincent J. Picozzi Jr, MD.

However, with the design of the Precision PromiseTM clinical trial platform, conducted by the Pancreatic Cancer Action Network (PanCAN), and a number of participating sites, experts in the field are hopeful that this new approach will be standardized across malignancies.

PanCAN announced the launch of Precision Promise, a unique, adaptive clinical trial platform for patients with pancreatic cancer on October 13, 2020. With this new framework, the investigational therapies can be tested in as a little as 3 years, and with a smaller number of patients. Furthermore, multiple agents can be tested simultaneously and there are lesser costs endured.

Patients may also have the opportunity to receive both first- and second-line treatment options in one clinical trial through Precision Promise.

Eligible patients with pancreatic cancer can enroll at 15 exemplary sites in the United States, some of which include Cedars-Sinai Medical Center, Dana-Farber Cancer Institute, and Memorial Sloan Kettering Cancer Center.

“The hope is that this clinical trial framework will be transformational in terms of how clinical research is conducted. We hope that this will become a new standard, not just in pancreatic cancer, but in all areas of oncology. This process enables multiple agents to be tested quickly and simultaneously, with less patients and lower costs,” Picozzi explained.

In an interview with OncLive, Picozzi, director of the Pancreas Center of Excellence, and a physician in the Division of Hematology-Oncology at Virginia Mason Medical Center, spotlighted the launch of PanCAN’s Precision Promise clinical trial platform, and how it is expected to impact clinical practice.

OncLive:Could you spotlight the prevalence of pancreatic cancer in the United States, along with the rationale behind this new clinical trial framework? 

Picozzi: In 2020, pancreatic cancer will affect more than 60,000 people in the United States. Notably, 1 person out of every 70 people, will develop this disease. Due to the difficulties faced when treating this disease, it actually represents that third leading cause of cancer death in the United States. It’s soon to be the second leading cause of cancer death in the United States, surpassed only by lung cancer.

In standard clinical trials, the agent, when in investigations, goes through 3 different phases. In phase 1, the toxicities, side effects, and the appropriate dose is determined. In phase 2, we look to see if the drug has a positive effect against the disease that is being tested. Finally, in phase 3, the drug is compared with the standard of care as part of a treatment regimen to see how effective it is compared with standard therapy. After passing all 3 phases, the drug will become a candidate for FDA approval.

The Precision Promise trial design is unique in a number of ways. First, it enables the testing of multiple agents simultaneously. Secondly, it allows the agent to be tested in different stages of the disease as it evolves. Thirdly, it combines the second and third phases of standard clinical trials to 1 phase. Finally, the trial has an adaptive design, meaning that the probability of the treatment being successful or not successful is recalibrated as the trial unfolds.

If you have a drug that seems to be working well, it receives a disproportionate number of patients that have enrolled to the trial. If you have a drug that's not working so well, it also receives a disproportionate number, but in a lesser way. Due to this, the drug is designed to succeed or fail more quickly, based on the weighting of the randomization. The whole process accelerates the ability to evaluate an agent.

Eligible patients can enroll at 15 different sites in the United States. On what basis were these sites selected?

There are 15 sites in the United States, many of which are premier sites in the country.

These sites were chosen competitively. One major criterion was a strong background or interest in pancreatic cancer research, the ability to accrue patients to the trial, and the ability to work together collaboratively. When looking at the roster, we truly have an all-star cast of participants.

What are some of the key challenges faced in the pancreatic cancer space? Do you believe this new clinical trial framework can mitigate any of these challenges?

Unfortunately, there hasn’t been a great track record of success in the development of drugs in this space. In addition, the drugs that have been approved by the FDA haven't had the impact, in all cases, that we would have liked. Our trial design addresses this challenge by making a more attractive opportunity for pharmaceutical companies to invest their drugs and resources in pancreatic cancer, by leveraging commitment over time, trying to ensure a higher probability of success, and including an improved pathway to regulatory approval.

Further, the trial tries to develop a linkage between basic science, laboratory science, and clinical science, which is where the name comes from. This is something that has been incompletely achieved in the space. Patients with pancreatic cancer undergo the most detailed testing ever done in the space and hopefully that, along with the trial design itself, will be a platform for drug development.

Finally, besides the wonderful doctors that we have, we have placed a great emphasis on supportive care. We are trying to standardize our supportive care approach to patients, to enable them to receive these drugs successfully across all 15 sites. We're actively doing research to try to advance supportive care in the field of pancreatic cancer. Therefore, this is a tool for patients to succeed.

For any of your colleagues in pancreatic cancer who are less familiar this new platform, what is important for them to know?

All investigators should be interested in maximizing the probability of success of what's been tested, and this trial achieves this in so many ways. In addition to its resource efficiency and its molecular and clinical sophistication in terms of the participants, it offers a new way of thinking about pancreatic cancer. It also offers a new collaboration of relationships between clinicians, the pharmaceutical industry, biostatisticians, the FDA, and the patient community, along with all other stakeholders.

I would also emphasize that the entire effort, which is sponsored by PanCAN, is trying to put the patients at the center of everything that happens. We are trying to give the patients the very best chance to succeed. In order to do that, the trial contains a number of innovations, making the testing and evaluation of drugs much easier.

Looking forward, do you believe other tumor types could benefit from a similar clinical trial framework?

I absolutely do. This trial, in some ways, is like the I-SPY trials in breast cancer. The hope that I have, as well as the FDA, is that this model will be beneficial for other tumor types as well, not just pancreatic cancer.

Reference

Pancreatic Cancer Action Network announces groundbreaking clinical trial platform transforming development of treatment options for world’s toughest cancer. News release. Pancreatic Cancer Action Network. October 13, 2020. Accessed November 19, 2020. https://bit.ly/2IQhq2b.