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NCI Program Explores Best Practices for Enrolling Underserved Groups to Precision Oncology Trials

Steven Gore

CHICAGO – A National Cancer Institute-funded study exploring strategies for diversifying clinical trials found community engagement, study navigators, and telemedicine showed promise in enrolling patients traditionally left out of research, but efforts to screen for and enlist study participants harboring specific biomarkers of interest weren't as successful.

In 2020, Sen. Richard Shelby, R-Ala., introduced a congressional mandate to fund a program focused on eliminating cancer research disparities. A supplement to the NCI Cancer Center Support Grants led to the formation of the Create Access to Targeted Cancer Therapy for Underserved Populations (CATCH-UP.2020) program and provided a $6 million one-year budget to fund eight cancer centers that had a demonstrated track record of recruiting underserved populations — including racial and ethnic minorities and socioeconomically and geographically disadvantaged patients — to clinical trials. Funded cancer centers were tasked with recruiting at least 24 patients to trials ongoing within NCI's Experimental Therapeutics Clinical Trials Network (ETCTN), and at least 50 percent of those recruited had to belong to an underserved group. 

The ETCTN inks cooperative research agreements with industry and research institutions in its network to develop and conduct early-stage clinical trials for innovative cancer drugs. But to qualify for the CATCH-UP grant, the cancer centers couldn't already belong to the ETCTN. The eight cancer centers selected to the program were housed at the University of California, Irvine; Wake Forest University Health Sciences; New York University Langone Health; University of Kansas Medical Center; University of Alabama at Birmingham; University of Miami; Dartmouth-Hitchcock Medical Center; and Wayne State University.

At the American Society of Clinical Oncology's annual meeting this week, Steven Gore, a medical officer in the Investigational Drug Branch within NCI's Cancer Therapy Evaluation Program, discussed best practices gleaned from these cancer centers in terms of outreach to underserved communities; coordinating with faraway trial sites; integrating telemedicine and other technology for administering precision medicine; and setting standards for outreach to comprehensive cancer centers. The cancer centers all had access to underserved communities, Gore noted, highlighting that the University of Miami has a large Latino population; Wake Forest University in Winston-Salem, North Carolina, serves rural and African American communities; and UC Irvine treats one of the largest Vietnamese enclaves in the US. Investigators involved in CATCH-UP described their experiences in JNCI Cancer Spectrum in February. 

From October 2020 to August 2022, the eight cancer centers enrolled 246 patients into 52 Phase I and Phase II ETCTN trials. These institutions had to show that they could routinely genomically test patients, because many of the trials conducted by ETCTN involve biomarkers for stratifying patients and determining best responders to investigational treatments. "It really was a precision medicine-oriented program," Gore said about CATCH-UP in an interview following his presentation at ASCO. "In the ETCTN, we tend to focus on genomically defined subsets."

For example, one clinical trial for which cancer centers in the CATCH-UP program were recruiting patients was focused on testing the activity of Novartis' Tafinlar (dabrafenib) and Mekinist (trametinib), and AbbVie's Bcl2 inhibitor navitoclax in BRAF-mutant melanoma and other solid tumors. Another basket trial of a glutaminase inhibitor focused on nerve sheath tumors with NF1 aberrations, and still another considered the efficacy of AstraZeneca's PARP inhibitor Lynparza (olaparib) in patients with IDH-mutant refractory acute myeloid leukemia and myelodysplastic syndromes.

The cancer centers had to screen 556 patients to enroll 246 participants evenly divided between males and females. However, 81 percent of the patients were white. Among the just under 20 percent of minority enrollees, 10 percent were Black or African American and 5 percent were Asian.

These trials were happening during the COVID-19 pandemic and investigators were tasked with enrolling "underserved populations," which, according to an executive order on advancing racial equity from President Joe Biden, includes not just minorities but also medically underserved and rural populations.

Accounting for all that, "we did well," Gore said, estimating that with the help of the cancer centers in the CATCH-UP program, the proportion of patients from underserved populations within ETCTN trials increased from 13 percent to about 23 percent. "It was still, by far, a majority white population," Gore acknowledged. Underserved populations "include white people, so there's nothing wrong with that," he went on. "But in our ability to really enrich for people of color and other traditional ethnic minorities, we came up short still. We have a long way to go."

The strategies that seemed to work best in enrolling underserved populations, Gore said, involved study navigators who spoke to patients in their own language, were culturally knowledgeable, and helped them navigate the clinical trials system; telemedicine and decentralized research operations; travel assistance; and immersion within underserved communities. He highlighted, for example, that the University of Miami helped La Liga Contra el Cancer, a cancer center that serves the Latino community, set up the ability to run clinical trials and recruit patients. The University of Kansas, meanwhile, used its expertise in telemedicine to remotely consent patients and got community doctors to administer drugs to patients in far-flung parts of the state. 

The cancer centers that were particularly successful in enrolling underserved groups all had very active community outreach offices and persistent investigators who shared what was and wasn't working in monthly calls. For example, the cancer centers that opened mostly Phase II trials seemed to be able to better meet CATCH-UP's enrollment goals than the sites that opened Phase I trials, which take much longer to accrue.

Some of the cancer centers' approaches to biomarker screening also didn't pan out. Gore described a kind of "brute force approach" some institutions tried, using research coordinators to sift through the genomic data and identify patients from underserved communities with biomarkers of interest in the clinical trials. "That was not really a successful approach," Gore reflected, because although research coordinators spent a lot of time screening for patients, it was too removed from patient care teams.

Gore explained in an interview that he and others had encouraged cancer centers in the CATCH-UP program to pick ETCTN trials that they knew they could accrue to based on the population they served. For example, if doctors at a cancer center weren't treating a lot of pancreatic cancer patients, then it would be best to avoid trials focused on that disease. Similarly, by working closely with teams focused on treating patients with specific diseases, investigators would be able to identify the types of biomarkers that were more prevalent in patients in that community and choose trials accordingly.

"You have to engage with the disease teams," Gore said. "It doesn't really matter if you have the best trial open in triple-negative breast cancer, if physicians have competing trials or don't want to do it; you're not going to accrue to that. It really is a big team effort." He suggested that an algorithmic approach for screening patients' electronic medical records for molecular markers of interest and then informing their doctors if they match to a therapy trial could work, and this is what is being attempted within the MyeloMATCH study. 

The highest performing institutions in terms of meeting CATCH-UP's enrollment goals, such as the University of Kansas and Wake Forest University, have gotten additional funds and have been made part of the ETCTN so they can teach other cancer centers in the network how to enroll underserved populations. NCI has formed additional equity-focused investigator teams who will also learn from the CATCH-UP program and be similarly tasked with increasing enrollment of underserved groups into other ETCTN trials.

It's important that these learnings ripple out to other cancer centers, Gore said, predicting that eventually it will probably be required of institutions that want to join ETCTN that they enroll underserved groups in their trials. "You've got to learn how to do this," he said. "It's not just a justice question, right? It really is a medical question."

Out of concern that the lack of diversity in clinical trials meant that drugmakers weren't generating evidence that their drugs were safe and effective in minorities receiving them, the US Food and Drug Administration earlier this year issued a draft guidance outlining its expectation that pharmaceutical companies will develop and submit plans for including adequate numbers of racial and ethnic minorities in their therapy trials.

Lola Fashoyin-Aje, who is leading the FDA's Project Equity to improve minority representation in clinical trials, suggested during a presentation at ASCO that the agency issued the latest guidance because industry hasn't really heeded its past calls to improve diversity in research. A 2018 study by Narjust Duma et al. in the Journal of Oncology Practice found a decrease in recruitment of minority patients into cancer clinical trials over the past 14 years compared to historical data, and that African Americans, Hispanics, and women were less likely to be recruited to such studies.

"There was a need to be very clear about FDA's expectations for diversity," Fashoyin-Aje said, adding that the discussions around diversity with industry for many years were very general. Now, the FDA is asking sponsors to specify enrollment goals and detail how they will meet them. "There weren't any discernable goals or plans to achieve [diversity], or any metrics to really be able to assess whether or not we're achieving these goals," Fashoyin-Aje said. "This is really the first time in FDA guidance where we've expressed an interest in knowing how the study population will be distributed and how it relates to the overall affected population."

Guidelines, of course, aren't legally enforceable on industry. Still, Gore lauded the FDA for seemingly putting its foot down and laying out its expectations for industry on this matter. "Sounds to me like they're very serious about it," he said, adding that it remains to be seen what effect it has on industry efforts.

Meanwhile, other cancer centers looking to emulate the success that the institutions in the CATCH-UP program had in enrolling underserved groups will have to make a monetary investment in the strategies that worked, such as hiring equity-focused investigators and nurse navigators, setting up telemedicine, and truly engaging with communities typically left out of research. A back-of-the-napkin calculation of the $6 million budget for the CATCH-UP program breaks down to $550,000 in spending for each cancer center's enrollment efforts and a per-patient accrual cost of $20,000.

"For an industry trial, that's really not so bad," Gore said. "For government … this is a lot of money. And that just says we need to spend more money [on equity in clinical trials] because this is the bare minimum. If the government is going to get behind this, we need to pony up."