For doctors who treat pancreatic cancer and for researchers who study the disease in hopes of better understanding its complex biology, one thing has been painfully clear: Patients need help now.
That’s why both the pancreatic cancer clinical and research communities are placing their bets on a new model for pancreatic cancer clinical trials called Precision Promise. Launched in the fall of 2016, with plans for first patient enrollment in July, 2017, Precision Promise is a nationwide precision-medicine endeavor focusing on patients and their individualized response to experimental treatment.
The trial is funded by an initial investment of $35 million raised by the Pancreatic Cancer Action Network. The organization’s goal is to double pancreatic cancer’s low survival rates by 2020, with a longer-term goal of continuing Precision Promise until a 50 percent five-year survival rate for pancreatic cancer patients is achieved.
According to the American Cancer Society, the five-year survival rate for patients with early-stage diagnoses of exocrine pancreatic cancer, the most common form of the disease, is only 14 percent. The majority of patients are diagnosed at later stages, and five-year survival rates for someone diagnosed with stage IV disease, for example, is an abysmal 1 percent.
Changing the Way Research Is Conducted
“These patients need new ideas, new concepts, and new treatments more quickly,” says pancreatic cancer expert Diane Simeone, M.D., co-chair of Precision Promise’s executive leadership committee. “And the only way we can do that is by changing the way we do things. We need to put patients at the center of our research.”
Although she has seen progress in the years she has been studying and treating the disease, Simeone, like others in the field, has been concerned about the difficulties faced when trying to get the scientific discoveries about pancreatic cancer from a laboratory setting rapidly into the clinical trial setting. Another major concern: the gold standard of randomization and controls, which has been a hallmark of clinical trial design, but did little to help individual pancreatic cancer patients.
“What we did was look at the challenges as real opportunities to change the way that science moves from the bench to the individual patient and, hopefully, positively affect the outcomes for these patients,” says Simeone, who was recently recruited as associate director for translational research and director of the new Pancreatic Cancer Center at New York University’s Langone Medical Center. Simeone’s laboratory at the University of Michigan’s Comprehensive Cancer Center studies the molecular mechanisms that drive metastasis, the leading cause of cancer death in patients. Her lab was the first to identify pancreatic cancer stem cells, a discovery that might explain why current drug therapies are ineffective against the disease. She also leads a team-based effort in new technologies for early detection in pancreatic cancer.
Precision Promise Patient-Centered Science
Precision Promise does indeed put patients at the center of a trial of experimental therapies. Here’s how it works.
In a Precision Promise trial, a patient’s doctor first figures out what chemotherapy agent is best for a patient, based on numerous factors such as the other diseases the patient may have, or their ability to tolerate treatment, among other considerations.
Then, based on the unique molecular profile of the patient’s tumor, that patient will join a Precision Promise sub-study. Based on the most promising science available, the initial three Precision Promise sub-studies will tackle pancreatic cancer from three different approaches: DNA damage repair defects, stromal disruption, and immunotherapy.
But unlike traditional trials in which patients are often not able to move between trials because of specific eligibility requirements, for example, patients enrolled in Precision Promise have options. All sub-studies are designed to allow patients to move on quickly to another sub-study if initial experimental treatment isn’t helping them. An innovative adaptive clinical trial design will be utilized to get answers faster about what is working, and what is not working, in individual patients. An exciting partnership is also being developed with numerous pharmaceutical companies so that all the agents needed for the trials will be available to pancreatic cancer patients.
“What we wanted to do was remove roadblocks for patients,” Simeone says. “The traditional approach to clinical trials was not working for these patients. There were too many barriers. As scientists we know that you can learn a lot about a particular therapy while still potentially benefiting a patient at the same time.”
The research teams will add new sub-studies based on the strength of data showing the potential of various new approaches. “This is collaborative and evidence-based, and this is what will bring new therapies to patients more quickly,” Simeone says.
Precision Promise launches with 12 Clinical Trial Consortium sites. These sites were selected by a peer-review process. Starting in the summer of 2017, participating patients will enroll in Precision Promise at a local Clinical Trial Consortium site. All data from the Clinical Trial Consortium sites will be securely collected and analyzed together so that scientific findings can be determined efficiently and shared quickly.
“Pancreatic cancers are increasing, but current survival rates are dismal. You need a new approach and a brave approach to not only advance the science but also to better help these patients,” Simeone says. “I have seen clinical trials come and go and I have had to witness patients not benefitting. I can honestly say this new approach makes me excited as both a scientist and a doctor who treats patients with this horrible disease. Our patients deserve to get the best evidence-based treatments quickly since that’s the only way we are going to improve survival.”
To learn more about Precision Promise, visit the Pancreatic Cancer Action Network website.