Community-Based Clinical Trial Enrollment Expands Access to Prostate Cancer Care

Although clinical trial opportunities are often recommended for patients receiving cancer care at academic centers, patients being treated in community settings are just as motivated to receive investigational treatments, provided they have sufficient access to this care, according to Gautam Jha, MD. Expanding clinical trial enrollment to include community centers is an exciting, patient-focused research advancement, Emmanuel Antonarakis, MD, added.

The phase 3 ECLIPSE trial (NCT05204927) evaluated 177Lu-PSMA-I&T vs standard-of-care hormone therapy (abiraterone acetate [Zytiga] or enzalutamide [Xtandi]) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressive disease and received prior treatment with an androgen receptor (AR)–directed therapy. The trial enrolled 439 patients with mCRPC and documented positive prostate-specific membrane antigen (PSMA) PET imaging. The M Health Fairview Ridges Cancer Clinic in Burnsville, Minnesota—in partnership with the Masonic Cancer Center, University of Minnesota in Minneapolis—was 1 of the study sites, and patients treated during this study were also enrolled from nearby community cancer centers.¹

“This partnership between the [community and the] university benefits everyone,” Jha emphasized.

In an interview with OncLive®, Jha and Antonarakis discussed the rationale and design of the ECLIPSE trial, efforts by community oncologists that boosted widespread accrual to this trial in Minnesota, and how partnerships between community and academic cancer centers can improve clinical trial accrual rates and increase patient access to cutting-edge, investigational therapies.

Jha is the medical director for the M Health Fairview Masonic Cancer Clinic and the Advanced Treatment Center at the M Health Fairview Clinics and Surgery Center––Minneapolis. He is also the chair of the cancer committee for M Health Fairview Ridges Hospital.

Antonarakis is associate director of Translational Research at the Masonic Cancer Center and the Clark Endowed Professor of Medicine at U of M Medical School.

OncLive: What was the purpose of the ECLIPSE trial? What did this trial evaluate, and what patient population was included?

Jha: The ECLIPSE trial [investigated] lutetium bound to a PSMA antibody in patients with mCRPC who had progressed on at least 1 novel anti-androgen therapy and were naive to previous chemotherapy with docetaxel. A similar agent, lutetium Lu 177 vipivotide tetraxetan [Pluvicto; formerly 177Lu-PSMA-617], has been FDA approved [for adult patients with PSMA-positive mCRPC] after novel anti-androgen therapy and docetaxel.² The ECLIPSE trial intended to see whether [patients could achieve more benefit if we] moved a similar agent up in the chain and provided this treatment option earlier.

Antonarakis: One of the most exciting treatments for patients with advanced prostate cancer in the past 2 to 3 years has been a radioactive therapy that is injected into the patient’s vein, instead of being administered as an external radiotherapy. This therapy was made safe and not toxic [through an] engineering step where the radioactive particle is engineered to bind to a protein that is expressed on the surface of the prostate cancer called PSMA.

The first drug [using this treatment approach] to become FDA approved was called lutetium Lu 177 vipivotide tetraxetan, made by Novartis. The downside of the current FDA approval of this medication is that for a patient to be eligible, they need to have received and progressed on both a novel hormone therapy—meaning a drug that blocks the testosterone receptor—and an intravenous chemotherapy. If we want to prescribe [lutetium Lu 177 vipivotide tetraxetan] to patients who have not received chemotherapy, it’s not reimbursed, and it’s not affordable for most patients.

The idea with the ECLIPSE trial [was to investigate] a similar agent. [177Lu-PSMA-I&T is] not identical [to lutetium Lu 177 vipivotide tetraxetan; it] has a different chemical structure. They are different drugs, but they have the same principle. Instead of waiting for a patient to progress on chemotherapy, to be closer to the end of life, and then give [radioligand therapy], why not give this instead to patients who have progressed on one or more hormone therapies, but have not yet received any chemotherapy? Most of these patients are fitter, healthier, and do not wish to receive chemotherapy because of the associated toxicities. This was the first trial in Minnesota and nearby states to offer a radioligand therapy to patients who did not have to go through chemotherapy first to be eligible for it.

The University of Minnesota and M Health Fairview community site had the highest global accrual to the ECLIPSE trial. How was this achieved?

Jha: One [reason] was the novelty of the treatment. Radioactive lutetium that is bound to PSMA is so targeted and specific for prostate cancer cells, so the toxicity is limited. The novelty of using a radioligand intravenously makes [the agent] promising and effective, and that had patients excited about it.

This [therapy and trial also] delayed the use of chemotherapy. For most patients [with mCRPC who had received a prior novel anti-androgen therapy], the alternative would have been to proceed with either chemotherapy or another novel anti-androgen therapy. The alternative of choosing chemotherapy is not as exciting for most patients. Patients would [often] rather volunteer for a clinical trial [investigating a] promising agent [such as 177Lu-PSMA-I&T].

Antonarakis: There was another important aspect [of this trial], and it was my great pleasure to collaborate with Dr Jha on this. A lot of university hospitals conduct clinical trials only within their own doors. For a patient to be eligible [for participation in the trial], they need to travel to that one academic center.

After discussing this trial with Dr Jha three years ago, when the trial came to our attention, we decided to do something a little different, which would be more patient-friendly and extend the reach of the clinical trial beyond the walls of the University of Minnesota. We decided to partner with community oncologists who have an affiliation with the university but are not university employees directly. Those oncologists, Dr Jha being the lead of that group, also see patients at several other physical sites throughout [Minneapolis and St. Paul]. To clarify, the treatment itself could only be given at the University of Minnesota because it was a specialized radioactive substance that had to be handled with care and certain safety precautions had to be followed. However, the identification of patients and discussions about this trial with eligible patients who could be candidates for it happened across multiple different sites.

Jha: This [enrollment strategy] helped us because patients often don’t want to always travel to the university. The university attracts the most motivated patients. Prostate cancer is one of those cancers that is commonly treated by community oncologists. [Most patients with prostate cancer] end up in the community rather than at university centers in many places, including the University of Minnesota.

In the community, we had access to [additional] patients. [For this trial], we teamed up with local oncologists. I passed on [information] and encouraged all my colleagues to reach out to me if they had patients who would be even remotely eligible [for the trial]. I was always willing to answer [questions] and evaluate the cases [to see whether patients would] qualify for the study. We encouraged [community oncologists] to send us patients. I traveled to multiple community sites that have predominantly genitourinary and prostate practices, [allowing us to] accrue patients unlike before.

Did this widespread patient accrual strategy match your expectations for this undertaking? What unexpected challenges did you encounter?

Jha: We did quite well in terms of accrual. We did better than what we would have expected. We continued accruing at the same pace [as we did when] we started, so we could perform this trial to our expectations.

The needs of patients in the community and the university are exactly the same. Everyone wants cutting-edge research; they want to participate in the latest [trials], but they are not necessarily willing to travel because that adds an unacceptable burden to family members, or other logistics are prohibitive.

[Additionally], oncologists in community practice are [often] busy with patient care, and putting patients on clinical trials is not on the top of their agendas. That hampers clinical trial enrollment. Most patients are then referred only after they have progressed on all lines of therapy, so trials that are designed to treat patients earlier [in the disease course] have challenges with accrual [in the community].

[In the ECLIPSE trial, patients were offered treatment with] a promising agent, and we could generate enough enthusiasm among other community colleagues, and I could reach out to them. I trained at the University of Minnesota, so I’m a local person, but all the neighboring hospitals and neighboring cancer centers have several oncologists who have been trained at [the University of Minnesota] and have colleagues who are either senior or junior to me. We could reach out to them and encourage them to send patients to us. We did well in terms of accrual. The patients and their referring oncologists were happy because the [referring oncologists] retained their patients but could provide cutting-edge therapy for them when they needed it.

References

1. 177Lu-PSMA-I&T for metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Updated February 29, 2024. Accessed March 4, 2024. https://clinicaltrials.gov/study/NCT05204927
2. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. News release. FDA; March 23, 2022. Accessed March 4, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer?utm_medium=email&utm_source=govdelivery