Trial Category: Prostate

This randomized, placebo-controlled phase III trial is evaluating the benefit of rucaparib and enzalutamide combination therapy versus enzalutamide alone for the treatment of men with prostate cancer that has spread to other places in the body (metastatic) and has become resistant to testosterone-deprivation therapy (castration-resistant). Enzalutamide helps fight prostate cancer by blocking the use of testosterone by the tumor cells for growth. Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors, such as rucaparib, fight prostate cancer by prevent tumor cells from repairing their DNA. Giving enzalutamide and rucaparib may make patients live longer or prevent their cancer from growing or spreading for a longer time, or both. It may also help doctors learn if a mutation in any of the homologous recombination DNA repair genes is helpful to decide which treatment is best for the patient.

Though androgen deprivation is initially effective in lowering PSA in the vast majority of patients, disease progression to metastatic castrate-resistant prostate cancer is a frequent event in men with high-risk biochemically relapsed prostate cancer, due to enhanced intra-tumoral ligand production and androgen receptor amplification.  Potent androgen signaling inhibitors including androgen synthesis inhibitors and next generation androgen receptor antagonists have transformed the management of metastatic castration-resistant prostate cancer, with improvements in progression-free and overall survival with both treatment approaches.