NEW YORK – Washington University in St. Louis has launched a research program focused on health disparities and barriers to clinical trial participation for patients with colorectal cancer, bile duct cancer, and multiple myeloma.
The program, which received $17 million in funding from the National Institutes of Health last week, will focus on genetic sequencing of African American patients with multiple myeloma and colorectal cancer, and patients of any race with cholangiocarcinoma, or bile duct cancer. The program will also interview these patients to identify barriers to participating in clinical trials, which could help design more inclusive studies in the future. The funding came through the National Cancer Institute's Cancer Moonshot program, and the project will be part of its research network focused on participant engagement and cancer genome sequencing.
The program, called the Washington University Participant Engagement and Cancer Genomic Sequencing Center, will enroll up to 900 patients around the US. Three researchers from Washington University's Siteman Cancer Center are leading different portions of the program. Ryan Fields, a surgical oncologist, will focus on patient recruitment and engagement; Bettina Drake, associate director of community outreach and engagement, will run the patient optimization portion of the study; and Li Ding, professor of medicine in the division of oncology and a professor of genetics, will lead the genome sequencing part of the program.
African American patients make up 20 percent of multiple myeloma cases, and the cancer is twice as common in Black patients than in white patients, according to the International Myeloma Foundation. In colorectal cancer, African Americans are 20 percent more likely to get the disease and about 40 percent more likely to die from it than most other groups, according to the American Cancer Society.
"We at Siteman are quite fortunate to have expertise across the spectrum of biospecimen science, cancer genomics, public health, and healthcare disparities research," Fields said. "We have a very unique catchment area with high rates of certain cancer types that have a high incidence of underserved and underrepresented minorities being studied."
The trial will initially partner with patient advocacy groups including Fight Colorectal Cancer, the Cholangiocarcinoma Foundation, and the Multiple Myeloma Research Foundation to boost enrollment.
The patient optimization aspect aims to understand barriers to clinical trial participation and genome sequencing among these populations. This group will conduct interviews with patients who have enrolled in the program and those who refused to participate to fine-tune its outreach strategy and identify barriers that could inform future clinical trial designs. The insights from these interviews will also be fed back into the patient engagement group to better attract new participants.
Minority patients are often poorly represented in clinical trials, which experts have attributed to a lack of trust in medical research and the healthcare system generally, along with other barriers like transportation, travel time, and the ability to take time off work.
"There's a lot of mistrust of the [healthcare] system and how their information might be used," Fields said. "There's also an element of cost and other burdens on the patient, such as where [clinical trials] are done, whether they're going to get stuck with a bill, or if it's going to affect the way they're treated."
Drake has assembled a patient advisory board, which includes leaders from the cancer type-specific patient advocacy groups and minority health advocates, including a leader from a Missouri-based nonprofit group Rare and Black. Drake hopes the board will offer the patient perspective and community expertise to the program.
The advisory board will guide the interview process of the program and review questions for any blind spots. Drake said they hope to gauge why participants decided to join the study, what they hope to get from having their genes sequenced, what they expect to come from the results, and whether they will share their results with family members.
The researchers will use a web-based tool called Genomics Adviser to educate patients about genomics research and collect information on their preferences.
"We're really interested in some of the ethical issues and the decision making that individuals might be going through when they're deciding to participate or after they've decided to participate," Drake said. "There was also some interest in how to inform the broader community about these types of cancers and genome sequencing, as well, not just reaching out to the study participants."
Once patients are enrolled, they will also undergo genome sequencing. The researchers will perform whole-exome sequencing, whole-genome sequencing, and RNA sequencing on patients. The program will use in-house CLIA-certified assays through Washington University's Genome Technology Access Center at the McDonnell Genome Institute.
By conducting several different types of testing, Ding hopes to capture both a deep and wide view of each patient's genome.
"We are also including RNA sequencing, because it is important for validating some of the actionable events coming out from the whole-exome sequencing and also for identifying druggable fusions that are important in cancer and are quite important to capture," Ding noted.
The researchers have also proposed adding in more types of assays to the program after the initial 900 patients are enrolled, including cell-free DNA sequencing, single-cell sequencing, and multiplex imaging.
The sequencing results will be returned to patients to help guide their treatment and will also be used to contribute to research about these understudied populations in the three cancer types. While there have been large-scale sequencing projects before, like NCI's The Cancer Genome Atlas, or TCGA, Ding hopes this program will provide deeper insights into areas that TCGA may have missed.
In multiple myeloma, the Multiple Myeloma Research Foundation is also conducting a large-scale genetic sequencing effort. The MMRF's CureCloud Research Initiative, which launched this year, aims to sequence about 5,000 individuals in the next five years by using at-home testing kits.
While TCGA is one of the largest sequencing efforts for colorectal and bile duct cancer, for cholangiocarcinoma other groups are continuing to explore biomarkers associated with the disease because of its rarity. This month, Memorial Sloan Kettering's Innovation Hub partnered with French biotech Owkin to use machine-learning approaches to discover prognostic biomarkers of response among bile duct cancer patients.
Based on TCGA's findings, drugmakers are developing biomarker-targeted treatments for both colorectal and bile duct cancer, yet sequencing disparities can hinder access to these treatments.
For example, Merck's pembrolizumab (Keytruda) was approved this year for microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer patients. However, a study published this year found there were disparities in who was being tested for microsatellite instability and mismatch repair deficiency. Colorectal cancer patients who were older or of Black non-Hispanic descent were less likely to receive testing than other groups.
Ding hopes that conducting more comprehensive sequencing methods compared to other efforts like TCGA, which began in 2006, will advance understanding of the three cancer types at the single-cell level and the tumor microenvironment level to help advance new treatments.
"TCGA and other large-scale studies have analyzed those three cancer types, but most of those efforts were focused on Caucasian patients," Ding said. "Since our focus is on understudied populations, we believe we can really enrich the landscape of these three cancer types [to better understand] significant mutated genes or driver genes in those three cancer types and populations."