As most of you know, in early December 2012, the FDA approved Abiraterone Acetate w/ prednisone prior to chemotherapy for the treatment of men w/ mCRPC. Coincidental to this approval, the Dana-Farber IST protocol changed wrt the combination trial of Abiraterone w/ Cabo.
The protocol change recorded at clinicaltrialsdotgov on 12/7/12 was from this...
"A Dose Finding Clinical Trial of Cabozantinib (XL 184) Administered in Combination With Abiraterone in Post-chemotherapy Castration Resistant Prostate Cancer ."
"A Dose Finding Clinical Trial of Cabozantinib (XL 184) Administered in Combination With Abiraterone in Castration Resistant Prostate Cancer."
This change really spiked my interest in this trial, as this places Cabo in one of it's earliest CRPC therapeutic applications in combination with the premier Janssen drug that stands to become the new SOC in prostate cancer therapy. I believe this change in trial protocol vastly improves the significance of the trial outcome for cabozantinib. I encourage you to put this one on your watchlist.
My last post of 2012. Chores done for the year, my wife and I are headed out to play cards w/ friends - our way of bringing in the New Year. Best of health, happiness, and prosperity to all in 2013.
Nice input. It is interesting what can be found by trolling through the clinicaltrials site and reading the changes. I agree with you that this means that they will be recruiting both pre and post chemo patients into this trial, I would hope that the next change also corrects the title of the trial to reflect this. The trial title still specifies post-chemo.
I would not look for meaningful data from this trial for a long time. It will be an ascending dose study, probably holding the abbie dose at the prescribed level and adjusting the Comet dose upward in stepped cohorts. A cohort size of 3 is a commonly used strategy. When they get an MTD (max tolerated dose) they will likely do an expansion cohort to better define if this is a good fit. I think it unlikely they will step higher than 60mg/day. The small numbers will make efficacy data almost meaningless, but the safety/tolerability information will be important.
Look for a similar study combining Comet with enzalutamide (MDV 3100 Xtandi). For background, Abbie is an enzyme that blocks hormone production and 3100 blocks binding at androgen receptor sites. It is now conjectured that abbie resistance is primarily driven by mutant androgen receptors that bind with the steroids given concommittantly with abbie and the PC community is anxiously awaiting a test of abbie/Xtandi given in combination.