Medivation, Inc. (MDVN) has formally begun its phase III trial of the investigational drug MDV3100 with men who have advanced prostate cancer. The clinical trial known as AFFIRM will evaluate the novel androgen receptor antagonist, MDV3100, in men with castration-resistant prostate cancer who were previously treated with docetaxel-based chemotherapy.
AFFIRM is a randomized, placebo-controlled, double-blind, multi-national trial that is expected to enroll approximately 1,200 men at sites in the United States, Canada, Europe, South America, Australia and South Africa. The primary endpoint of the trial is overall survival (the FDA’s gold standard). The secondary endpoints include progression-free survival, safety and tolerability.
MDV3100 works as an anti-androgen drug like bicalutamide (casodex) and it has shown to have an approximately five fold higher binding affinity for the androgen receptor (AR) compared to the commonly used antiandrogen, bicalutamide (casodex).
Referring to the phase I and II studies, the study’s principal investigator Howard Scher, MD, Chief of the Genitourinary Oncology Service and the D. Wayne Calloway Chair in Urologic Oncology at Memorial Sloan-Kettering Cancer Center said, “… the declines in PSA observed at these lowest doses are encouraging and provide proof of concept that castration resistant prostate cancers can still be sensitive to alternative hormone therapies like MDV3100.”
Yet we do not know if PSA reductions will correlate with an improvement in overall survival, the standard endpoint used in this pivotal Phase 3 studies for hormone-refractory prostate cancer. Only time will tell.
 Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, Sawyers CL (May 2009). “Development of a second-generation antiandrogen for treatment of advanced prostate cancer”. Science 324 (5928): 787–90. doi:10.1126/science.1168175. PMID 19359544.2 Scher HI, Beer TM, Higano CS, Taplin M, Efstathiou E, Anand A, Hung D, Hirmand M, Fleisher M (2009). “Antitumor activity of MDV3100 in a phase I/II study of castration-resistant prostate cancer (CRPC)”. J Clin Oncol 27 (15s): abstr 5011. https://web.archive.org/web/20120224004203/http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=34746.
Joel T Nowak, MA, MSW
Had my monthly appointment Friday at MSKCC. Learned that they are putting final touches on protocol to expand Phase III trial to chemo naive patients. Look for official announcement early 2010.
Read your insert, are you on the MDV 3100 3rd Trial ? Would be keen to know, I started in South Africa in middle May, after having Radiation and CHemo. Looks positive that I am on the “active” tablet, my PSA has dropped 95% in first month, side effects minimal, but extreme fatique in later part of the day.
Would be interesting to hear from you, and how you are getting on.
Peter South Africa
Thanks for asking about how I am doing. A short update – my PSA is continuing to rise. As of the beginning of June it made it to 1.47 and is doubling at a rate of a little over 5 months. My guess is that at the next oncologist appointment I will schedule some scans, I project the PSA to have made it to around 2.35 at that time. Then, if the scans are negative I will probably go back to hormone therapy at the following appointment (projected PSA of around a PSA of 4.0). I feel great.