A new model for cancer clinical trials was launched Tuesday for patients with pancreatic cancer, one of the most deadly types of cancer. Called “Precision Promise,” this new nationwide precision-medicine endeavor seeks to turn the concept of clinical trials on its head: Rather than finding participants for a given experimental treatment study, the approach finds the right treatment for a given patient at a given time.
This effort hopes to offer a “better” way to treat patients with experimental therapies, said Dr. Sunil Hingorani, a pancreatic cancer physician-scientist at Fred Hutchinson Cancer Research Center and principal investigator for one of Precision Promise’s initial 12 sites.
“This is driven by doing what is best for the individual patient, and that is the most important thing. For the first time, in a very real sense, we are going to be working with the patients to tackle this disease together,” said Hingorani, who is also a member of Precision Promise’s eight-member nationwide executive committee.
Precision Promise, which expects to enroll its first participants in the spring of 2017, is a clinical trial. But its design is a departure from that of traditional trials. The Precision Promise trial creates a fluid structure through which participants can transition in and out of numerous substudies of various experimental treatment approaches, depending on their tumor’s unique and shifting biology.
The trial is funded by an initial investment of $35 million in philanthropic funds raised by the Pancreatic Cancer Action Network, an organization aimed at doubling the disease’s abysmal survival rate by 2020. The percentage of patients who survive for five years after an early stage diagnosis of exocrine pancreatic cancer, the most common type, is just 14 percent, according to the American Cancer Society. The rate plummets for the many patients who are diagnosed at later stages.
“Precision Promise will dramatically accelerate the clinical trial process to bring promising therapies to patients faster,” said Julie Fleshman, president and CEO of the Pancreatic Cancer Action Network in a prepared statement.
The trial works like this: When a participant enrolls in Precision Promise, the study team will capture the unique genetic information and details of the proteins present in that patient’s tumor. Based on that molecular profile, the patient will be enrolled into the substudy of the particular experimental therapeutic approach that holds the most promise to combat their cancer. Later, if that option doesn’t seem to be working, the patient can shift to another substudy’s experimental treatment, without having to seek out and enroll in a new trial. Data from all study sites will be shared centrally so that collaborating researchers throughout the entire network can learn from each participant.
Seattle is home to two of Precision Promise’s initial two sites: one led by Fred Hutch’s Hingorani and another a couple of miles away at Virginia Mason Medical Center, led by pancreatic cancer specialist Dr. Vincent Picozzi.
The launch of Precision Promise “is a huge moment,” said Picozzi. “If it works out the way we hope, it will completely change how pancreatic cancer research as a whole is pursued nationwide.”
University of Michigan pancreatic cancer expert Dr. Diane Simeone has seen a great deal of progress made in this disease in the decades she has been studying it. Despite these advances, however, she and others in the field were frustrated by the roadblocks that prevented the best science from transitioning quickly from lab bench to clinical trials, she said.
The scientist saw this problem as an “opportunity to change the clinical trial infrastructure in the U.S., much for the benefit of patients,” she said. Simeone became one of the leaders of the effort and now co-chairs Precision Promise’s executive leadership committee.
A classic tenet in medicine is that the “gold standard” of clinical research is the randomized controlled trial ― a trial in which each participant is randomly assigned to receive either the experimental treatment or a comparison treatment. For studies enrolling cancer patients, the comparison treatment is nearly always the standard of care. With randomization and control groups, researchers can glean clear cause-and-effect relationships between a particular treatment and patient outcomes.
Precision Promise’s design is a radical departure from this classic model: There is no randomization and no traditional control. While this might raise eyebrows in the scientific community, it is a good thing, Hingorani argued, to subordinate “the pure scientific rigor of an intellectual experiment done in a vacuum” to the immediate needs of patients diagnosed with pancreatic cancer.
“The primary critique is ‘You’re not randomizing.’ And that’s exactly right. Because ‘random’ is the same as flipping a coin, which is a powerful way to do science but harder to justify when considering an individual patient’s life,” he said.
Because each participant will undergo extensive testing as their tumors react to the various therapies they might receive through the trial, “the patient becomes their own control, in a sense,” Hingorani said, offering researchers insights into the effects of the treatments despite the lack of a traditional control arm.
This is a type of “adaptive trial design,” in which investigators are free to modify the trial parameters in a prescribed way as new knowledge emerges from an ongoing trial.
Adaptive trials are underway for other tumor types, including breast cancer, and at least one ongoing adaptive trial, which enrolls patients with a variety of advanced cancers, also allows participants to switch from one experimental arm to another. Precision Promise is the first such trial focused solely on pancreatic cancer.
“We believe that you can both learn, in a deep way, about the strategy you’re applying and actually maximally benefit that patient at the same time. We don’t want to wait three to five years to find out if Drug XYZ is going to work for Patient ABC, because they won’t be here three to five years later,” Hingorani said.
As pancreatic cancer research progresses, the team will add new substudies to the trial based on the strength of preclinical evidence pointing to the potential of each new approach. This collaborative, evidence-based decision-making process for advancing new therapies to the clinic sets this study apart, Simeone said.
She pointed to the extensive inter-organizational collaboration as another unique feature of the trial. Industry is providing the experimental drugs being tested in the substudies. An initial group of four biomedical companies is partnering in the effort, sharing expertise and participating in trial design. The study team also expects that the number of research sites will be expanded in the coming years, possibly even to include international collaborators, Simeone said.
“With the increasing incidence of pancreatic cancer and survival still in the single digits, we felt we needed to provide leadership and be brave enough to change the strategy in which we do clinical trials,” Simeone said.
Despite everything that’s new about this research model, it’s also quite obvious, Hingorani said.
“On one hand, it’s incredibly ambitious, and on the other hand it’s exactly where we need to be to treat this cancer,” said Hingorani, who lost his father to the disease.
His father’s death was the impetus for his single-minded focus on overcoming this cancer, he said.
“Clarity comes from being forced to encounter this disease at a level you never thought you would ― basically, having a loved one taken away from you. Everything else pales in comparison,” he said.
“All that matters to me is what we’re doing now to change this.”
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Editor's note: This story was revised after publication to reflect the fact that Precision Promise is not the first adaptive trial to allow participants to switch mid-trial to a different experimental treatment.
Susan Keown is a staff writer at Fred Hutchinson Cancer Research Center. Before joining Fred Hutch in 2014, Susan wrote about health and research topics for a variety of research institutions, including the National Institutes of Health and the Centers for Disease Control and Prevention. Reach her at email@example.com or follow her on Twitter at @sejkeown.