New Trials in Prostate Cancer: Could Your Patients Benefit?

A number of studies in prostate cancer have started enrolling in recent months. Perhaps one of your patients could benefit from enrolling in one of these trials?

Unfavorable intermediate-risk prostate cancer.  Patients who have received this diagnosis in the previous 12 months can join a phase 2 study that avoids androgen-deprivation therapy (ADT). The usual approach for such patients is ADT plus radiation treatment. The trial is, instead, testing two different levels of stereotactic body radiation therapy (SBRT) guided by the Decipher score, a genetic measure that assesses the likelihood of the tumor spreading.

All participants will receive SBRT to the seminal prostate and seminal vesicles every other day. Men with high-risk Decipher scores will also receive radiation to any dominant lesion within the prostate and to the lymph nodes in the pelvis. The sole outcome measure is progression-free survival (PFS) over 2 years as assessed by PSA. Overall survival (OS) and quality of life (QoL) will not be tracked. Memorial Sloan Kettering Cancer Center (MSKCC) has seven sites across New Jersey and New York that started recruiting 145 participants in December. More details at clinicaltrials.gov.

Commenting on the MSKCC study, Marc Garnick, MD, professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, who is not an investigator in the trial, said that the lack of randomization may mean that the study “may not move the field forward in helping determine if ADT is or is not needed in this population.”  

Unfavorable intermediate-risk prostate cancer. Men with this diagnosis can also join a National Cancer Institute (NCI)-partnered phase 3 study that takes a randomized approach to the question of whether ADT — along with its devastating side effects — can be avoided in men with low-risk Decipher scores. The trial will also hope to improve prospects for high-risk men by adding darolutamide (Nubeqa), a medication for castration-resistant prostate cancer, to ‘usual therapy’ of radiation plus ADT.

Low-risk participants will receive up to 11 weeks of radiation treatment plus up to 6 months of ADT (ie, usual therapy) or radiation alone. All men with high-risk Decipher scores will receive usual therapy; one group will also receive daily oral darolutamide. The study opened in November, hoping to recruit 2050 participants across 14 US states. Development of metastasis is the primary outcome; OS and QoL are secondary outcomes. More details at clinicaltrials.gov.

Garnick commented that this study is “potentially important” and “makes a lot of sense as long as the specific criteria for low- vs high-risk genomic classification is adhered to and homogeneous among the study populations.”

Prostate cancer that has spread to the bones. Adults with this type of prostate cancer who have already undergone a prostatectomy or ‘definitive radiotherapy’ are sought for a phase 2 trial testing the addition of radium (Ra-223) dichloride to SBRT. One group of men will receive a ‘sandwich’ of two doses of Ra-223 over 4 weeks, followed by a week’s worth of radiation, then four doses of Ra-223 over 16 weeks. Participants in the control group will have radiation only. The study opened in November and aims to enroll 136 participants across Colorado, New Jersey, New York, and Ohio. PFS is the only outcome measure. OS and QoL will not being tracked. More details at clinicaltrials.gov.

Because Ra-223 is already indicated for metastatic prostate cancer to the bone and there is no comparator, Garnick said he was “not sure what meaningful data will emerge in a 136-patient study: Will hematological toxicity be evaluated and compared to historical controls?”

Advanced-stage prostate cancer. Men whose prostate cancer has lodged in five or fewer other locations are eligible for an NCI-sponsored phase 2 study looking at the benefits of adding oral therapy with the gonadotropin releasing-hormone antagonist relugolix (Orgovyx, Relumina) to usual radiation therapy. All participants will receive 1-3 weeks of radiation; people in the experimental arm will also take relugolix tablets for 6 months. The trial began recruiting 269 participants in December in Illinois and Michigan. The primary outcome is PFS; OS is a secondary outcome and measures of QoL apart from sexual function and fatigue will not be assessed. More details at clinicaltrials.gov.

“This study makes sense for patients who do not want to have the obligation of coming in on a periodic basis for injections of ADT,” Garnick said. However, the results “are likely to be descriptive if there is no comparator arm to compare efficacy or safety.”

Chemotherapy-naive metastatic castration-resistant prostate cancer. People with this type of prostate cancer who have received at least one novel anti-androgen are sought for a phase 2 study testing BMS-986218, an investigational monoclonal antibody engineered to enhance the anti-tumor immune response. For up to 2 years, participants will receive either chemotherapy standard docetaxel (Taxotere); docetaxel plus BMS-986218; or the two-drug combo plus immunotherapy nivolumab (Opdivo). The study started in February and aims to recruit 204 men worldwide. Sites in 18 states are planned. ‘Incidence of death’ over 2 years and OS over 4 years will be recorded; QoL will not. More details at clinicaltrials.gov.

Metastatic castration-resistant prostate cancer. Patients in this situation who have a positive prostate-specific membrane antigen (PSMA) result on PET imaging are being sought for a phase 3 trial of the new radioligand lutetium Lu-177 vipivotide tetraxetan (Pluvicto; formerly referred to as 177Lu-PSMA-617), which has just been FDA approved.

This product was designed to deliver minute doses of radiation to cancer cells, sparing healthy tissues. Men in the control group will receive standard-of-care hormone therapy. Participants in the treatment group will receive up to four treatments of Lu-177 every 6 weeks for several months or until disease progression (the primary endpoint for all patients). OS and QoL are secondary endpoints. Study sites across 14 states hope for 400 participants; centers in Florida, Michigan, Nebraska, and Texas opened their doors in February. More details at clinicaltrials.gov.

Garnick said this trial is an “important study that will add to the expanding utility of Lu-177 in this patient population.” He added, “Hopefully there will be correlative studies to further the precision of sites of responsiveness to Lu-177 and [the] level of PSMA positivity at entry.”

All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov). Garnick reports no conflicts with any of the trials. He is editor-in-chief of the Harvard Medical School Annual Report on Prostate Diseases, for which he receives an honorarium. 

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