Molecular model of abiraterone
Two recently approved drugs for the treatment of advanced prostate cancer—radium-223 (Xofigo) and abiraterone acetate (Zytiga)—will be studied in combination in a phase III clinical trial. The trial (NCT02043678) of abiraterone with or without radium- 223 has begun enrolling men with castration-resistant prostate cancer that has spread to bone, not yet been treated with chemotherapy, and is causing no or mild symptoms, according to a description on the website Clinicaltrials.gov.
The endpoint of the randomized, double-blind, placebo-controlled study will be symptomatic, skeletal, event-free survival at 3 years, or, more specifically, whether the addition of radium-223 to standard abiraterone will prolong life and delay the time to skeletal-related events such as painful fractures or bone pain, according to the website.
Secondary endpoints include overall survival, time to opiate use for cancer pain, time to pain progression, time to cytotoxic chemotherapy, radiological progression-free survival, and number of participants experiencing adverse events.
The trial could help urologists unravel some of the mystery surrounding how to best combine or sequence the half-dozen new therapies for advanced prostate cancer that have been approved by the FDA since 2010, including abiraterone and radium-223.
Radium-223 has been shown to delay the time to a patient’s first skeletal-related event, as well as to prolong survival, in patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease. Abiraterone has been shown to prolong survival men with metastatic prostate cancer in whom the disease has progressed while receiving treatment with androgen deprivation therapy.
The trial is expected to enroll about 800 patients at 150 centers, with a study completion date of July 2020 and the collection of final data for the primary outcome by July 2017.
Patients will be randomized in a 1:1 ratio to receive either radium- 223 or placebo in addition to abiraterone acetate plus prednisone/ prednisolone, in combination with best supportive care, for the first 6 cycles, followed by abiraterone acetate plus prednisone/ prednisolone thereafter. Treatment will continue until an on-study symptomatic skeletal event occurs or other withdrawal criteria are met, the website explained.
The study is sponsored by Bayer in collaboration with Janssen Research & Development, LLC.
Clinicaltrials.gov. National Institutes of Health. Radium-223 dichloride and abiraterone acetate compared to placebo and abiraterone acetate for men with cancer of the prostate when medical or surgical castration does not work and when the cancer has spread to the bone, has not been treated with chemotherapy and is causing no or only mild symptoms (ERA 223). Clinicaltrials.gov. http://tinyurl.com/qew8l58. Published January 1, 2014. Updated May 8, 2014. Accessed June 4, 2014.