The purpose of this open-labeled, randomized study is to compare any good and bad effects of using a life-prolonging alpha emitting therapy, radium-223 (Xofigo®), along with a life-prolonging taxane-based chemotherapy, docetaxel, versus using docetaxel alone in men with castration-resistant prostate cancer (CRPC) with bone metastases. This combination aims to address a critical need to improve survival, to delay disease progression, and to relieve pain, preferably with a more favorable safety profile than existing treatments, in this population.
There are currently six active therapies for the treatment of metastatic CRPC (mCRPC). As a standard, most patients will either progress through abiraterone or enzalutamide. After first line therapy for mCRPC, patients will largely be resistant to further androgen receptor (AR) directed therapy. Chemotherapy at this point, using docetaxel, has a well-established role in this clinical context, even after abiraterone and enzalutamide resistance. The other treatment options are radium-223, Sipuleucel-T and cabazitaxel. However, the magnitude of the overall survival benefit is modest for mCRPC.
The hypothesis of targeting both the host organ of metastatic disease with a bone-seeking radiopharmaceutical like radium-223 and targeting the tumor itself with chemotherapy is predicated not only on the concept of multicompartment targeting. These two agents may well also cross-sensitize, as chemotherapy may enhance the effects of the radioactive energy emitted by radium-223, and radium may enhance the cytotoxic effects of chemotherapy. The safety of the sequential administration of full dose docetaxel followed by radium-223 was definitively established in the phase III ALSYMPCA trial (ClinicalTrials.gov Identifier: NCT00699751). The DORA trial was developed in response to promising results from an earlier PCCTC study of radium-223 and docetaxel (ClinicalTrials.gov Identifier: NCT01106352), also led by Dr. Morris. DORA will enroll a maximum of 738 subjects across approximately 30 sites in the US and the Netherlands.
For additional information on the DORA trial please visit ClinicalTrials.gov.