Johnson & Johnson Innovative Medicine is recruiting a Phase 3 clinical study, called LIBERTAS, to explore several questions about metastatic prostate cancer. The twist is that the company is actively looking for transgender volunteers to evaluate, making it the largest, and one of the only, oncology studies of its kind.
LIBERTAS researchers will evaluate the clinical risk factors and underlying biology of prostate cancer, specifically to determine whether patients who reach an undetectable level of chemical biomarkers for prostate cancer—prostate specific antigens or PSAs—could have their cancer therapy cut back without risking escalation of the cancer.
Prostate cancer is diagnosed in nearly 300,000 people in the U.S. every year, according to the National Cancer Institute, and claims nearly 35,000 lives annually. What’s known about prostate cancer is based on cisgender men, however. The LIBERTAS study, developed in partnership with LGBTQ+ groups at Johnson & Johnson and external patient advocate groups including Fenway Health, is attempting to broaden the understanding of prostate cancer to include all people with prostates, which includes transgender women.
Regarding trans women in the study, LIBERTAS researchers want to know whether patients with newly diagnosed metastatic prostate cancer can safely stop taking androgen deprivation therapy (ADT), a treatment for prostate cancer that stops the growth of cancer cells by lowering the amount of androgens (male sex hormones). ADT is a common part of gender-affirming hormone therapy for suppressing masculine secondary sex characteristics like facial hair, and it complicates the prostate cancer risk assessment for trans women.
Not much is known about the risk of prostate cancer for trans women. A 2023 study indicated that the chances of prostate cancer in trans women may be higher than previously thought, and that patients on gender-affirming hormone therapy (GAHT) had the most aggressive cancer, possibly due to delayed diagnoses. Because testosterone is fuel for prostate cancer it would make sense that GAHT would lower the risk of cancer, but researchers determined that the relationship between female hormones and prostate cancer is more complicated, and may lead doctors to misinterpret “normal” PSA levels in people on gender-affirming hormones—levels that have been based on data from cisgender men. Right now, there are no PSA ranges for trans women. A working theory is that current prostate cancer testing may give trans women a false sense of assurance, possibly due to the complicating factor of GAHT.
“We are recruiting anyone who has an intact prostate where the cancer has spread to different parts of the body,” said one of the LIBERTAS researchers, Neeraj Agarwal, MD, professor of medicine and senior director for clinical translation at the Huntsman Cancer Center in Utah.
“So we are not excluding anyone based on how they look. Second, [transgender] patients may have gotten androgen deprivation therapy or testosterone-lowering therapy in the past, and if they have prostate cancer, it may be more aggressive prostate cancer [because] the major driver was not there and they still had prostate cancer. So, do they have different biology?”
Agarwal speculated that they might respond differently to treatment compared to cis men with prostate cancer.
Another benefit of the study, Agarwal added, is that it will encourage investigators across the world to not exclusively use the word “men” when referring to people with prostate cancer. “We want to improve the awareness of transgender people, and we specify that this trial is transgender inclusive. And know many of these individuals are never diagnosed in a timely fashion or treated well. Anyone who has an intact prostate—and it doesn’t matter how they look, how they dress, how they behave—the trial will include them. I think it is a major step forward.”
The struggle for trans inclusivity in clinical studies
“The biggest story is we don’t know enough, and that is specifically because there has been a willful lack of data collection about our [transgender] population,” said Scout, PhD, MA, executive director of the National LGBT Cancer Network and member of the Johnson & Johnson prostate cancer patient advocacy steering committee. “So we are almost always left to hypothesize based upon the data points we have.”
“Right now we know that trans women are at risk for prostate cancer, but do we know how the hormone interactions affect that risk for prostate cancer?” Scout said. “Trans women have a huge level of discrimination in our society in the first place, and I know way too many who don’t even have routine access to health care, who would anticipate that… trans women are most often finding their cancer much later than the rest of the population, and when they do so, they have very few treatment options, and their limited access to health care in the first place is probably going to further limit those options.”
But Scout admitted that without the kind of data LIBERTAS can provide, that’s still a theory. The goal should be, he said, to design clinical studies that account for all variables that affect health outcomes. “So if you are continuing to say, ‘this medicine is going to work great with the people with this genetic combination, and all the people we tested on were cis, straight, white guys with this genetic combination,’ that doesn’t mean you can say in the general population… that this treatment will work well with them, because you’ve got other variables you haven’t looked at.”
Designing and conducting more inclusive studies requires extra effort and money for recruitment, plus a determination to do things differently, advocates say.
Recently the U.S. Food and Drug Administration (FDA) issued preliminary guidelines urging greater diversity in clinical studies. Though it didn’t single out transgender or nonbinary people, trans advocates take this as a sign the tide may be turning toward greater inclusivity. If so, it’s a change that’s been a long time coming.
“We see an increased desire to include trans people in clinical trials largely due to long-term advocacy from the trans community demanding inclusion,” said Eli R. Green, CSES, who uses the pronouns he and they, and is the founder and principal of Trans Affirming Training & Consulting and consultant on the LIBERTAS study.
“We also have more trans people and allies in the medical fields who are raising the question of why trans folks are not already being included, and how to change that. The FDA mandate is helpful, but without folks who are dedicated to understanding how their work impacts (or omits) transgender, nonbinary and intersex people, nothing much changes.”
The lack of diversity in study design, he said, has its genesis in medical school. “We know that in medical school, most students never receive any formal education on human sexuality as a whole, let alone the experience of people who fall outside the gender binary. So, in many cases it literally never occurs to folks designing the studies to include transgender, nonbinary and intersex people in their work.”
When it comes to clinical trials, there are two primary areas of need, he said. “First is that many cisgender folks have no idea what it is like to be a trans person trying to engage in medical care or related systems, so we help them to understand the additional barriers that transgender, nonbinary and intersex people face and identify skills and strategies for removing or mitigating those barriers.
“Second is better understanding how to fit transgender, nonbinary and intersex people into medical systems that are designed based on the idea that sex and gender are a binary,” he said. For clinical trials, this means having guidance on things like how to interpret lab values or inclusion criteria that align with the study goals.”
Green and other advocates see one barrier in implementing inclusive clinical trials: physicians and staff often not trained on how to engage with trans people in ways that are positive and affirming.
There are some recent data showing the extent of discrimination against trans and gender nonbinary people. Nearly one-quarter of respondents in the 2022 U.S. Trans Study reported that in the previous 12 months they did not see a doctor when they needed to due to fear of mistreatment. Of those who saw a healthcare provider within the last 12 months, nearly half (48%) reported having at least one negative experience due to being transgender, including misgendering, harsh or abusive language and even physical abuse or refusal to treat.
We are recruiting anyone who has an intact prostate where the cancer has spread to different parts of the body
Such experiences lead to a mistrust of primary care physicians and discourage trans and gender nonbinary people from participating in trials. Scout said that researchers designing inclusive trials must take extra steps to combat “well-earned medical mistrust” by some populations.
“I’m talking with a lot of clinical trial sponsors, and they say they’re not getting any referrals from the existing pool of enrollment sites,” he said. “Well, you may be concentrating on enrollment sites and haven’t done good work around combating structural discrimination with a lot of populations. So a lot of what we do is say, ‘it isn’t so complicated.’ You need to take some steps to de-gender your clinical protocol. You need to then put out a modest amount of affirming information to say they’re going to be safe.”
Cultivating a diverse population for studies and clinical trials could not only lead to better science, but it also means more people will have better care and better treatments, Scout added. “They won’t have to wait until five years after the medicine finally comes out. They will get the same kind of access the most privileged people in our society can as they sign up to be part of the clinical trials before the medicines are even on the street.”
LIBERTAS has 90 locations throughout the U.S. TO READ the requirements for participating, GO TO clinicaltrials.gov/study/NCT05884398#participation-criteria. Eligible prospective participants can EMAIL Participate-In-This-Study@its.jnj.com for consideration.