Making Clinical Trials Easier

WHEN JULIE CLAUER WAS DIAGNOSED with stage IV colorectal cancer in 2018 at age 43, she knew it would be a tough haul. Over the next two years, a team of doctors at the University of Southern California Norris Comprehensive Cancer Center in Los Angeles treated her cancer with five open surgeries and 50 rounds of chemotherapy. She and her doctor also discussed the potential of enrolling in a clinical trial. By July 2020, the chemotherapy’s side effects were increasing while the number of platelets in her blood was dropping. If her health status and platelet counts continued to decline, she could have become ineligible for clinical trials, so they intensified the search.

Clauer’s cancer type, called microsatellite stable, typically doesn’t respond to immunotherapy, but she and her doctor found a clinical trial testing a combination of a checkpoint inhibitor immunotherapy drug and a tyrosine kinase inhibitor targeted therapy that appeared to stabilize the cancer in some patients. “I went into it with a different goal than most people go into trials with,” Clauer says. She was looking to take a break from chemotherapy for a few months while keeping her cancer in check. “That sounded fantastic to me.”

In the process, her cancer went from 11 tumors that could not be removed to four tumors that could. After being on the trial for 2 1/2 years, she and her care team decided she was ready for surgery to remove tumors that remained in her lungs. That meant she had to exit the trial, but she moved to an off-label use of Opdivo (nivolumab) and Yervoy (ipilimumab), two checkpoint inhibitor immunotherapy drugs, after cancer detected in some of her lymph nodes began to grow.

Expanding Eligibility

Clauer’s experience has made her an advocate for connecting more patients with clinical trials. For years, researchers have lamented low patient interest in clinical trials, but research by Joseph Unger, a biostatistician and health services researcher at Fred Hutchinson Cancer Center in Seattle, and his colleagues determined that more than half of cancer patients are willing to enroll in a clinical trial if one is available for them. In a March 2021 review published in the Journal of the National Cancer Institute, Unger and his team looked at 35 cancer clinical trials and found that Black, Asian and Hispanic patients were just as likely to enroll in clinical trials as white patients, contradicting the conventional notion that clinical trials lack diversity because patients from underrepresented groups are leery of participating.

Throughout his career, Unger has been inspired by patients’ enthusiasm for clinical trials and their efforts to help other patients find better treatment and support. “To me those are all important findings because it really appropriately gives credit to patients for their passion for clinical research and their willingness to contribute to that endeavor for themselves and future generations,” he says.

Unger says two roadblocks to clinical trial participation are trial location and eligibility requirements. “Most patients get their treatments in a community setting, but most of the trial work has been done in large academic centers,” he says, which are often located at major universities or in big cities. This obstacle can be a particular hardship for patients living in underserved communities where community health care sites often lack resources to support clinical trials, he says.

Patty Spears, now a research manager and patient advocacy leader at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center in Chapel Hill, has been advocating for patients since she was diagnosed with an aggressive HER2-positive breast cancer in 1999, when she was working as a microbiology researcher. At the suggestion of an immunologist colleague, she started searching for a vaccine clinical trial after undergoing chemotherapy and surgery. As a researcher, she knew how to navigate multiple clinical trial sites, but “it was really hard to get on a study,” she says. Spears tried to enroll in three different trials but wasn’t eligible for two of them because she didn’t know the number of positive lymph nodes she had before starting chemotherapy and her cancer didn’t have a certain necessary biomarker. Eventually, she was able to enroll in and travel to a Seattle-based vaccine trial despite being barely over the minimum white blood cell count the researchers required.

As a result of her experience, Spears says, “I’m really into eligibility criteria.” She points to new efforts to loosen eligibility criteria as a way to expand the pool of patients available for trials. For example, the phase III Pragmatica-Lung Study, which is testing a combination treatment for advanced non-small cell lung cancer, has fewer and simpler eligibility requirements. Researchers hope the trial, launched in March 2023, will accrue patients faster and better represent the real-world patient population. In addition, the trial has streamlined the number of tests and the amount of data collected from participants and is looking at a straightforward question—whether a specific immunotherapy treatment helps people live longer than standard chemotherapy.

Better Ways to Navigate Trials

Developing better ways to search for clinical trials based on eligibility and location is the goal driving several initiatives launched by patients and their supporters. If you go to clinicaltrials.gov, a clinical trial database and search engine, and look for trials that are recruiting or about to recruit patients for neuroendocrine tumors within a 200-mile radius of the San Francisco Bay Area, as Josh Mailman did recently, 67 trials pop up. Yet Mailman, who was diagnosed with neuroendocrine tumors in his pancreas and liver in 2007, notes that very few searches, even with added search filters, return relevant results that are specific to his type of neuroendocrine tumor.

Between too much information and not enough tailored searching ability, Mailman says, the current system has “an overwhelming amount of information for patients and many providers that make clinical trials not accessible and not discoverable.” Mailman, a patient advocate who co-chairs the National Cancer Institute’s Patient Advocate Steering Committee, wants clinical trial searches to be more personalized and easier for patients to conduct. Other efforts driven by patients and their supporters include cancer-specific search engines through advocacy groups like the Bladder Cancer Advocacy Network and support offered to patients as they search for trials like the Jason Carter Clinical Trials Search and Support Program, which focuses on blood cancers.

Mailman works with Ancora, a free, artificial intelligence-powered search tool through which people can tailor searches for clinical trials in 15 cancer types by answering questions about prior treatments, current health, geographic location and other details. Danielle Ralic, Ancora’s founder, says the company partners with people like Mailman, who helped spearhead a group of patients and oncologists to review Ancora’s endocrine tumor search process to ensure the search engine asked questions relevant to patients’ needs.

Ralic has seen how challenging it can be to navigate the health care system. With a background in technology and health care, she became the “health care friend” for her family and community. Now she wants to use technology to make it easier for more people to access clinical trial information. The Ancora website gets about 250 visitors a week searching for trials. People can set geographic preferences to access nearby trials and dive deep into their disease type, subtype and treatment history to narrow down the search. The company’s patient health team helps three or four people each week apply to trials by doing the legwork of contacting trial sites and pharmaceutical companies on the person’s behalf.

Ralic says she can’t calculate how many people enter trials based on what they find on Ancora because of the website’s privacy controls, but some who contact her after using the site say they print out the results for their doctors to start a conversation about trial options. “I hope there are a lot of those conversations going on,” she says.

Making the System Better

Even if a person is eligible for a clinical trial, there might be other hurdles to overcome. While major costs associated with treatments under study are usually waived for patients in clinical trials, they can still face additional expenses and logistical challenges, including time and money spent traveling to appointments. These obstacles can prevent a willing person who meets the eligibility criteria from taking part in a trial.

Spears at UNC Lineberger Cancer Center thinks the clinical trials system needs to be turned on its head to improve patient participation. Instead of forcing people to look for trials, she believes the research community should bring trials to people. “We can’t put the burden on the patient anymore,” she says. “You need to make sure every patient, empowered or not, has equal access to clinical trials.”

The COVID-19 pandemic brought changes to health care that could make it easier to take part in trials. For example, clinical trial participants who once had to go to the clinic for oral chemotherapy could now have medications delivered to their home. Spears, who was diagnosed with liver cancer in early 2022, says that while specialized tests might call for visits to a particular clinic, many tests can be done locally. “A liver MRI is a liver MRI,” she says. “I think it’s time for a change, and it’s perfect timing with COVID ending. How can we make the system better moving forward?”

Mailman, who has participated in clinical trials, was a faculty member for the July 2023 ASCO/AACR Methods in Clinical Cancer Research Workshop, which was aimed at teaching young investigators how to design and run clinical trials. (The American Association for Cancer Research [AACR] publishes Cancer Today.) Mailman helped researchers understand how to make trials more accessible by going over every aspect that affects patients, from whether the question their research is asking is relevant and understandable, to drawing out a grid of the trial’s schedule so patients don’t need to make unnecessary trips to the lab. “If I’ve done my job,” he says, “[the trial they develop] should be patient-friendly, not too intrusive, ask an appropriate question and be able to be completed.” 

Playing the Long Game

Using her experience with clinical trials and expertise gained from a career in marketing, Clauer now leads a course for Colontown, an online resource for people with colorectal cancer, that teaches patients how to search for clinical trials. In the course, Clauer emphasizes that patients should consider clinical trials as part of a long-term strategy to manage their cancer, rather than as a last-ditch effort to save their lives. She helps people get up to speed on clinical trial terminology. She also stresses that they should consider their values, risk tolerance and what they are willing and able to do, from travel to surgery, as part of a trial. Clauer compares gathering information about possible trials to lining up planes on the runway, an analogy coined by another colorectal cancer patient advocate. If you get to a point where you need another treatment option or when new circumstances require a shift in your approach to cancer, you’ll have another option ready for takeoff.

Clauer is playing the long game herself. She continues to take the Opdivo-Yervoy therapy combination, and in June 2023, scans showed that the cancer in her lymph nodes had disappeared. She encourages the patients she works with to see clinical trials as building blocks that form their cancer treatment journey and to broaden their view of a good trial outcome. Stable cancer or improved quality of life may not compare with no evidence of disease, she says, but they are positive results nonetheless. “It’s a relay race,” she says. “[A trial] might be the silver bullet that saves you, but it could also be the one that saves you by getting you to the next treatment.”

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