Clinical trials are currently exploring new, better ways to find and kill pancreatic ductal adenocarcinoma (PDAC) cells so that people with the disease can live longer lives. Every chemotherapy drug, targeted therapy, and newer treatment approach available today first had to go through the clinical trial process before doctors could prescribe it. Clinical trials are crucial for advancing treatments for metastatic PDAC (mPDAC), which currently has no cure.
If your cancer diagnosis is new – or even if it isn't – the thought of taking part in a clinical trial may sound risky, or you may feel unsure that you have a role in these types of studies. But when it comes to advanced pancreatic cancer treatments, the importance of clinical trials can't be overstated, says Anna Berkenblit, MD, chief scientific and medical officer at the Pancreatic Cancer Action Network (PanCAN).
"They're fundamental," she says. "Without the clinical trial research process, we wouldn't have any of the drugs that we do have today that are helping people. So we encourage everyone to consider clinical trials as part of their treatment options."
Here's what to know about clinical trials for mPDAC, including what researchers are studying, how to decide whether a trial may be right for you, and questions to ask your doctor.
How Clinical Trials Are Moving mPDAC Treatments Forward
For many years, treatment options for mPDAC have been limited. Surgery and radiation won't work for most cases of mPDAC because of the spread of the cancer. Chemotherapy is the standard treatment doctors choose to help keep the cancer under control.
Now researchers are studying newer treatments that target specific changes inside pancreatic cancer cells. One of the biggest areas of focus is mutations in the RAS gene family. RAS helps control how your cells grow and divide. Normally, it works like a switch that turns cell growth on and off when needed. But when RAS is mutated, the switch can get stuck in the "on" position, causing cells to keep growing out of control and form cancer.
Over 90% of pancreatic cancers have a RAS mutation called KRAS. Current clinical trials are working on developing drugs that can turn these genes off, or inhibit them. These newer drugs are starting to reshape treatment, Berkenblit says.
"The most advanced RAS inhibitor is daraxonrasib [Rasonque], and that was studied through clinical trials from the first-in-human study to a randomized phase 3 study that just showed that it doubles overall survival in patients with previously treated metastatic pancreatic cancer," Berkenblit says.
The FDA has approved daraxonrasib to treat the most common form of pancreatic cancer that has spread to other parts of the body. Daraxonrasib blocks RAS proteins, which fuel cancer cell growth. By shutting down these proteins, daraxonrasib can slow cancer cell growth and may cause cancer cells to die.
Researchers are now trying to figure out how to make treatments work even better and longer.
"A RAS inhibitor by itself is not going to cure people," Berkenblit says. "It prolongs survival, but unfortunately, resistance develops."
That's why current clinical trials are studying combinations such as:
- RAS inhibitors plus chemotherapy
- RAS inhibitors plus immunotherapy
- RAS inhibitors plus other targeted drugs
- Cancer vaccines
- New biomarker-driven therapies
"We're trying to figure out what strategies are best to either overcome resistance or prevent resistance," Berkenblit says.
Researchers are also studying immunotherapy approaches for pancreatic cancer. Immunotherapy has transformed treatment for some other cancers, but pancreatic cancer has been harder to treat this way.
Scientists are now testing vaccines and immune-based combinations that may help the immune system better recognize pancreatic tumors.
Clinical Trials: Risks and Rewards
Many people assume clinical trials are only for people who have run out of options. But that's not true.
"In the olden days, there was no expectation that patients would benefit from trials," Berkenblit says. "It was all just about figuring out the dose and the safety profile. But now, because we understand the biology of cancer so much better and we have targeted therapies, it is not unreasonable to expect therapeutic benefit from participating even in an early-phase clinical trial."
Many newer trials test treatments that have already shown promise in earlier research. Some trials compare a new treatment to the current standard treatment. Others add a new therapy on top of standard care rather than replacing it. Usually, trials focus on a treatment that will add to existing treatments.
"You're getting therapy that we know works, plus it may do even better than what you could have with available therapies outside of a clinical trial," Berkenblit says.
This also means that the risks you take on in a clinical trial are very similar to any risks the standard treatments have. Your clinical trial team will talk to you beforehand about what to expect.
"The doctors, nurses, and research assistants will walk you through what's called the informed consent process," Berkenblit says. "They will describe what's involved in the clinical trial, how often you need to come in, what the potential risks are, and how to manage side effects if they were to occur."
When you're in a clinical trial, typically you have more careful monitoring than you would under standard care. That may look like more visits, more blood tests, or more radiology tests.
"Some people find that extra attention an added benefit of participating in a clinical trial," Berkenblit says.
Navigating Clinical Trial Enrollment
Every clinical trial has eligibility requirements. You have to meet these requirements to be considered for the study. These help researchers understand who the treatment may help and who may have a higher risk of side effects. One way researchers select people for clinical trials is through biomarker testing.
Biomarker testing looks for genetic mutations or other features on your tumor that may guide treatment decisions or help match you with a clinical trial. Berkenblit encourages every person with mPDAC to get tumor testing.
"That is an important part of just understanding what your standard treatment options are, as well as clinical trial options," she says.
Researchers also want to make sure the potential benefits outweigh the risks.
"If someone is super, super sick, it's probably not a great idea to participate in a clinical trial," Berkenblit says.
Finding clinical trials
Talking to your doctor is a good first step toward finding a clinical trial. You can also search ClincalTrials.gov to see a list of all the clinical trials in the U.S., although this can be an overwhelming amount of information at once, Berkenblit says.
"I would encourage patients to call PanCAN because we are the leading patient advocacy organization and we have a clinical trial finder with case managers who can walk you through every step of your journey," she says.
A case manager can help you understand what options you have, both standard-of-care treatment options and clinical trials, including what's in your area, and assistance with things like transportation and parking.
"Not every trial is open everywhere," Berkenblit says. "So there's considerations around geography and whether you can travel."
Questions to Ask Your Doctor
If you're thinking about a clinical trial, talk to your cancer care team.
You can ask:
- How do I get biomarker testing?
- Are there trials that fit my tumor type or mutations?
- What is the goal of this trial?
- How does this treatment compare with standard treatment?
- What side effects should I expect?
- How often will I need appointments or scans?
- Will I need to travel?
- What costs are covered?
- Can I leave the trial if I change my mind?
- How might this affect my quality of life?
Show Sources
Photo Credit: E+/Getty Images
SOURCES:
Anna Berkenblit, MD, chief scientific and medical officer, Pancreatic Cancer Action Network (PanCAN).
Moffitt Cancer Center: "What Is Metastatic Pancreatic Cancer?"
Therapeutic Advances in Gastroenterology: "Pancreatic cancer: why is it so hard to treat?"
Lustgarten Pancreatic Cancer Research: "From Undruggable to Unstoppable: The State of KRAS Drug Development in Pancreatic Cancer."
Dana-Farber Cancer Institute: "Center for RAS Therapeutics Clinical Trials and Research."
National Cancer Institute: "Clinical Trial Facts."
