A new Phase 3 clinical study, the EORTC trial 1333, will compare the combination treatment of enzalutamide and RA-223, versus enzalutamide alone, in the overall survival of patients with castration-resistant prostate cancer metastatic to the bone.

Androgen deprivation therapy, which includes several types of hormonal therapy, is usually used to reduce the levels of male hormones (androgens). This type of therapy, called ADT, is generally divided between treatments that lower androgen levels, such as surgical castration and Luteinizing hormone-releasing hormone (LHRH) analogs, and treatments that stop androgens from working. Often, however, patients become resistant to ADT (castrate-resistant). The standard of care for these patients now includes enzalutamide (Xtandi), a newer type of anti-androgen compound that blocks signals for cell division and growth occurring after androgens bind to the androgen receptor. This therapy delays treatment with chemotherapy, reduces pain, and helps improve or maintain quality of life, while bettering overall survival. Metastatic castration-resistant prostate cancer often derives from two important features, the continuing stimulation of the androgen receptor pathway and the ability of tumor cells to grow where bone remodeling has been disrupted.

RA-223 (Xofigo), used in the later stages of disease, targets bone metastases, the primary site of metastatic events in early castration-resistant prostate cancer patients.

The Phase 3 EORTC trial 1333, coordinated by the EORTC Genito-Urinary Cancers Group in collaboration with the Academic and Community Cancer Research United and the Ireland Cooperative Oncology Research Group, plans to enroll 560 patients at 59 institutions in 10 countries to study the effect of the enzalutamide and RA-223 combination versus enzalutamide as stand-alone therapy to improve patient survival.

Professor Silke Gillessen, study co-coordinator, explained its planning and objectives in a press release. “The combination of enzalutamide and RA-223 could attack two important features of metastatic castration resistant prostate cancer. Enzalutamide prevents androgens from binding to their receptor, and RA-223, by mimicking calcium, targets areas of bone metastases. The fact that the safety profiles of both drugs for the most part do not overlap and both treatments are generally well tolerated makes them interesting combination partners.  Furthermore RA-223 offers an additional mechanism of action when combined with enzalutamide that is approved for this indication, which makes them a potentially effective combination, too,” Dr. Gillessen said.

The trial, NCT02194842, is now open and enrolling patients. More information is available through this link to its ClinicalTrials.gov site.