Accoring to a Bloomberg Businessweek report and information on the Exelixis corporate web site, the company is planning two multi-center, randomized, Phase III clinical trials of the investigational agent cabozantinib (a.k.a., XL184) in metastatic, castration-resistant prostate cancer (mCRPC):
- The first trial (the ’306 trial) will enroll 246 patients with mCRPC that is evident in bone. The patients must have moderate to severe bone pain despite optimized narcotic medication, and they must have failed prior treatment with docetaxel and abiraterone (in no particular order). The trial will be carried out in “English speaking regions including the United States, Canada and the United Kingdom.” Patients will be randomized 1:1 to receive either cabozantinib or mitoxantrone + prednisone. Alleviation of bone pain will be the primary endpoint. Overall survival will be a secondary endpoint for this trial. Exelixis expects to start to enroll patients in this trial before the end of 2011.
- The second trial (the ’307 trial) will be initiated some time in the second half of 2012 and “is expected to be a global trial powered to evaluate overall survival time comparing cabozantinib versus prednisone in patients who have failed prior docetaxel and abiraterone.”
It appears that there were some differences of opinion between the U.S. Food & Drug Administration (FDA) about the precise conduct of the ’306 trial, and that — as a consequence — Exelixis will not be able to conduct this trial under a so-called “special protocol assessment” or SPA. We have no information about the details of this difference of opinion.
The last drug to be approved for pain management in patients with metastatic prostate cancer was mitoxantrone, back in the 1990s. It is somewhat suprising to see Exelixis seek an initial approval for such an indication, but they may feel that it is the fastest way to get data that would allow for the approval of cabozantinib and that can be carried out in a relatively small number of patients.