A Phase 3 clinical trial evaluating darolutamide (ODM-201) as a treatment for castration-resistant prostate cancer patients at high risk for metastasis is expected to conclude in September 2018, Orion, the therapy’s maker, announced.
This multicenter, randomized Phase 3 trial is evaluating darolutamide versus a placebo in non-metastatic castration-resistant prostate cancer patients at high risk for metastasis. The trial was designed to enroll 1,500 participants across 400 clinical centers worldwide. Patients will receive treatment twice daily until they develop metastasis or for up to six years.
Patients must have not received prior second-generation androgen receptor inhibitors, CYP17 enzyme inhibitors (which prevents steroid synthesis), chemotherapy, or immunotherapy. Treatment with bisphosphonates or denosumab — therapies that prevent bone damage — in the 12 weeks prior to randomization were also excluding factors.
The trial’s primary goal is to determine if patients on darolutamide live longer without developing metastasis compared with those receiving placebo. Researchers will also assess if darolutamide extends patients’ lives, delays symptomatic skeletal problems, and delays the need for chemotherapy. The amount of time to pain progression, along with the therapy’s safety and tolerability, will also be evaluated.
In laboratory studies, darolutamide showed a great affinity toward the androgen receptor, blocking its activity and preventing the growth of prostate cancer cells. In contrast with other androgen receptor inhibitors, the medicine showed minimal penetration of the blood-brain barrier.
Patients in these studies were given darolutamide doses ranging from 200 to 1,800 mg, and assessed for a prostate-specific antigen (PSA) response, which is defined as a 50% reduction or more in serum PSA levels. Phase 1 results showed that 81% of patients had a PSA response at week 12.
The therapy also had a long-term effect on PSA levels, with patients showing a median time to PSA progression of 19.3 to 72.3 weeks, depending on prior treatments. Responses were more significant in patients who had never had chemotherapy or CYP17 inhibitors, such as Zytiga (abiraterone acetate).