The SPIDERMAN trial investigates the combination of supraphysiologic testosterone therapy and darolutamide as first-line treatment for men with metastatic hormone-sensitive prostate cancer (mHSPC). This approach builds upon the concept of bipolar androgen therapy (BAT), which involves alternating between high and low testosterone levels to exploit the androgen receptor’s adaptive responses.

The BATMAN study explored BAT in mHSPC patients by initiating with androgen deprivation therapy (ADT) for six months, followed by alternating 3-month intervals of BAT and ADT alone. Results indicated that BAT was safe and more patients remained sensitive to hormone therapy after 18 months compared to expectations with ADT alone. These findings suggest that BAT can prolong the effectiveness of hormone therapy in mHSPC.

The SPIDERMAN trial aims to determine if combining BAT with darolutamide can further extend the response duration and reduce side effects. Darolutamide is an androgen receptor inhibitor that, unlike other similar drugs, has a minimal effect on central nervous system activity, potentially reducing side effects like seizures. The trial will also assess the impact of this combination on quality of life, gene expression, and metabolic changes associated with the therapy.

Clinical trial.