Clinical trials for pancreatic cancer remained open at NYU Langone Health’s Perlmutter Cancer Center during the peak of the 2019 coronavirus disease (COVID-19) pandemic so that new treatment options were available. A person at NYC Health + Hospitals/Bellevue with stage IV pancreatic cancer that had progressed after an initial treatment with chemotherapy was referred to Despina Siolas, MD, PhD, an assistant professor in the Department of Medicine. Dr. Siolas was able to enroll the patient as the first participant in Precision Promise℠, a nationwide innovative pancreatic cancer clinical trial. There are currently 15 cancer centers around the country participating in the trial, with a goal of enrolling thousands of patients.
“We have a multidisciplinary team that meets and prioritizes people with cancer who need clinical trials,” Dr. Siolas says. “We worked with our colleagues at Perlmutter Cancer Center’s Clinical Trials Office who, despite the difficult situation, were able to help us do all the paperwork and get the patient on the trial with the sponsor. Because this trial involves a lot of research capabilities, including biopsies, we were fortunate to be able to coordinate between the Clinical Trials Office and our laboratories and staff to facilitate this during the COVID-19 pandemic.”
Dr. Siolas is a member of Perlmutter Cancer Center and its Pancreatic Cancer Center, which strives to offer clinical trial options to all people with pancreatic cancer treated there, with clinical trial options for almost every category of patient.
“All of our team members consider clinical trials for our patients, and we go over the clinical trials that are available on a regular basis,” says Diane M. Simeone, MD, the Laura and Isaac Perlmutter Professor of Surgery in the Department of Surgery and director of the Pancreatic Cancer Center. “This is a perfect example of Dr. Siolas recognizing that this patient would be eligible and pushing it through even in the difficult times.”
Bridging the Gap Between Research and Treatment
Precision Promise℠ is a platform for testing novel treatments for first- and second-line patients, people with metastatic pancreatic cancer who have a new diagnosis or who have not responded to an initial round of chemotherapy. The trial was conceived four years ago by Dr. Simeone with the Pancreatic Cancer Action Network (PanCAN).
“We weren’t making significant advances in survival for pancreatic cancer,” says Dr. Simeone, who is the national principal investigator for Precision Promise℠. “And what became clear is that a sizeable gap exists between exciting laboratory research and developing a therapy that can change the care of people with pancreatic cancer. Part of this gap was based on limitations in how we conducted clinical trials for people with pancreatic cancer.”
Dr. Simeone proposed a map for improving pancreatic cancer clinical trials to PanCAN. The result was Precision Promise℠, an adaptive platform trial based on a number of tenets, Dr. Simeone says. First, there is a need for a novel model for cooperation among different centers, as well as with drug companies, the U.S. Food and Drug Administration (FDA), clinicians, and patients. Second, data sharing is crucial. Third, researchers need to be able to test novel drug combinations more rapidly to identify treatments that work and get them to the FDA for approval more quickly. If regimens do not work, researchers need to dispense with them quickly and move on to treatments that are more promising. Finally, Precision Promise℠ requires biopsies before and during treatment to help researchers understand why treatments work in some patients but not in others.
Precision Promise℠ is designed to conduct trials in much less time and at much less cost than conventional cancer clinical trials. There are common control arms, so fewer patients receive standard of care therapy. Multiple therapies can be tested simultaneously, enabling researchers to learn more about the experimental regimens more rapidly. An important feature, Dr. Simeone notes, is that Precision Promise℠ is a trial that can lead to FDA approval with far fewer patients than traditional clinical trials require.
“Because we have so many centers around the country working together, we were able to partner with the leadership of the FDA and build a consortium with the pharmaceutical industry, which had been hesitant to apply new promising therapies to pancreatic cancer,” Dr. Simeone says. “But by building the Precision Promise℠ platform, we were able to bring well over 30 pharma companies to the table. This has been an amazing effort from colleagues all over the country and the world.”
For the second-line phase of the trial, participants are randomized to either standard of care chemotherapy or experimental arms of a novel treatment regimen. The first experimental arm uses an investigational drug called SM-88 in combination with three other drugs: methoxsalen, phenytoin, and sirolimus. SM-88 targets mucin 1, a protein produced by the MUC1 oncogene that is overactive in most cancer cells and acts as a barrier against the immune system. Multiple additional experimental arms are currently being finalized and will soon be available to those eligible for the trial, Dr. Simeone says.
The trial also includes a supportive care research component, which includes how to best treat pain, help with nutrition, and monitor activity and sleep.
“We have a large research team studying all those critical issues in the context of the patients on these trials,” Dr. Simeone says. “The data that we are going to collect in helping us improve pancreatic cancer care globally are going to be quite remarkable.”