The next article is the 2008 publication of the recommendations of the Prostate Cancer Clinical Trials Working Group (PCWG2). Their recommendations are slanted more toward phase 2 trial design rather than endpoints for pivotal trials, but it is still a good starting reference. The group chose Dr. Scher as the corresponding author and it is not coincidental that he is collaborating with EXEL on the design of the first pivotal trial using a proposed pain/bone scan endpoint.
Color me an optimist, but my read of the results was that the bar that was set for success fell pretty short of what is being achieved to date with CABO.
Is that your impression?
"Results The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur."
Below confirms rational for unblinding the data.
"Conclusion PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit."
<<Color me an optimist, but my read of the results was that the bar that was set for success fell pretty short of what is being achieved to date with CABO.
Is that your impression?>>
It's a complex situation. First, the 2004 workshop and then the 2007 working group recommendations were FDA supported events, but the recommendations that come out do not carry the weight of formal policy. The FDA has an overall guidance document on acceptable oncology pivotal trial endpoints and in addition they plan to publish specific guidance documents for each general indication.
The overall "Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics" is still the official governing document for determination of appropriateness of various endpoints for trials designed to lead to drug approval. The article below discusses the past history.
I see almost zero probability that the CRPC expansion cohort can merit a subpart H approval. I see a good chance that Scher's proposed pain/bone scan composite endpoint will be acceptable. The caveat is that it has been a long time since FDA approved an oncology drug based on pain relief and it is a subjective observation and vulnerable to bias. We will have to see how this turns out. Hopefully they will nail it down with a special protocol assessment prior to starting a trial.