ust 3 percent of adult cancer patients participate in clinical trials of experimental treatments. In a novel effort to boost that number, a national nonprofit is launching an unusual study — one that allows patients to move easily between several experimental therapies, without spending precious time trying to find and qualify for a new trial if the first one doesn’t help.
Once they’re in, they’re in.
“The current clinical trials system doesn’t match what a patient needs,” said Julie Fleshman, president and CEO of the Pancreatic Cancer Action Network, which organized the $35 million “Precision Promise” platform announced on Tuesday. “This is all about doing that.”
The new approach raises some tough questions. It might be harder, for instance, to tease out the safety and efficacy of a treatment if patients shift from one to another. The trial aims to get around that obstacle by focusing on “progression-free survival,” or how long patients survive without the original tumor spreading. They will rapidly switch to another treatment if the cancer starts growing.
“It is a tricky trial design and there will be grey areas,” said Lynn Matrisian, chief research officer of the pancreatic cancer network. “This is a ‘signal-seeking’ trial so we are willing to accept some fuzziness in the data and are finding a balance between rigor and patient-centricity.”
Precision Promise will launch in the spring; it’s envisioned as the first large-scale precision medicine trial for pancreatic cancer. About 42,000 people in the United States are expected to die of pancreatic cancer this year, making it the country’s third-leading cause of cancer deaths. The prognosis is dismal: Only 8 percent of patients are still alive five years after being diagnosed.
Patients who enroll in Precision Promise will undergo molecular profiling of their tumor to identify mutations driving the malignant cells to proliferate. The hope is that researchers might find a targeted therapy to home in on those mutations and stop the spread of the cancer.
That’s a big “might.”
Pancreatic cancer hasn’t benefited from targeted therapy the way other diseases have. One reason: it’s very difficult to get a good sample of cancer cells from a pancreatic tumor. (The malignant cells tend to be few in number compared to inflammatory and other cells, making it challenging to isolate them.) As a result, relatively few targetable mutations, let alone targetable mutations for which drugs exist, have been identified, a 2015 study found.
That lack of options is reflected in clinical trials for pancreatic cancer.
Although more than 600 are listed in the federal database Clinicaltrials.gov, the vast majority test standard treatments such as surgery, chemotherapy, radiation, or some combination. “Maybe 10 percent, at most, are molecularly driven,” Matrisian said. “The revolution we’ve seen in other kinds of cancer has been very slow to reach pancreatic cancer.”
In the Precision Promise trial, a physician will first determine which chemotherapy “backbone” is best for each patient, based on the presence of other diseases, their ability to tolerate specific side effects, and how frequently they can come in for treatment.
Then the molecular profile of the tumor or characteristics of the area surrounding the tumor (its “microenvironment”) will determine which substudy a patient joins, explained Dr. Robert Vonderheide of the Abramson Cancer Center of the University of Pennsylvania, who is leading Penn’s part of the study. For instance, if they have a mutation in the BRCA2 gene, they might also be put on drugs called PARP inhibitors, which are used in other types of cancer.
The novel part is what happens next. If a patient does not respond to the first line of treatment, or relapses after initially responding, she can switch to a different sub-study without having to qualify for another clinical trial — an onerous process that can often involve traveling to a different city. In this case, no matter which sub-study a patient’s tumor characteristics qualifies her for, “all of them will be available at every site, so if a patient is in Florida or Philadelphia they can stay there,” said Vonderheide, whose center sees about 350 pancreatic cancer patients each year. He hopes to enroll them all in Precision Promise.
Traditionally, patients must meet various criteria to enroll in a new trial; if they’ve been previously treated with a similar drug or if they have additional illnesses such as cardiovascular disease, they may not qualify. Precision Promise does away with those barriers.
Precision Promise is starting with three experimental protocols but will eventually have more, Matrisian said, including immune-based therapies like those that are transforming the treatment of melanoma and non-small cell lung cancer.
“For the first time, in a very real sense, we are going to be working with the patients to tackle this disease together,” said Dr. Sunil Hingorani of the Fred Hutchinson Cancer Research Center, who will lead the study there. “Ultimately, we’d like to see this as a template for how you take care of every pancreatic cancer patient, at every site across the country.”